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Current Concepts Review - Interbody Fusion Cages in Reconstructive Operations on the Spine*

PAUL C. MCAFEE, M.D., TOWSON, MARYLAND

	Introduction

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
During the last five years, surgeons around the world have inserted more than 80,000 lumbar interbody fusion cages; in the United States alone, an estimated 5000 such devices are implanted each month. The recent interest in performing lumbar interbody arthrodesis with use of cages is attributable to three factors: the high rate of failure associated with use of bone graft alone^{3,22,26,45,46,71,82,84,94,96,106,107}; the high rate of failure associated with use of posterior pedicle-screw instrumentation^39,97,102; and the high rate of success associated with use of so-called stand-alone anterior fusion cages and autogenous bone graft, obviating the need to perform a 360-degree (combined anterior and posterior) lumbar arthrodesis with use of posterior instrumentation⁷⁷.

The purpose of the current review is to summarize the information in the literature with regard to the background, rationale, indications, techniques, results, and possible future developments of interbody arthrodesis for reconstruction of the spine.

	Background

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
Early techniques of arthrodesis with use of allograft or autogenous graft and without instrumentation were associated with a high rate of failure. In a classic study, Stauffer and Coventry⁹⁶ reported on eighty-three patients who had had an anterior interbody arthrodesis between 1959 and 1967. Of seventy-seven patients who were followed clinically for an average of 3.75 years after the procedure, twenty-eight (36 percent) had good (76 to 100 percent) relief of pain, fifteen (19 percent) had fair (26 to 75 percent) relief, and thirty-four (44 percent) had poor (0 to 25 percent) relief. Thirty (44 percent) of sixty-eight patients who were evaluated radiographically at a minimum of eighteen months postoperatively had a pseudarthrosis. Stauffer and Coventry defined radiographic fusion as "a pattern of continuous trabeculae traversing the grafted region and the adjacent vertebral bodies, with no evidence of motion when the patient was bending." These results, and the equally unfavorable results reported by other investigators^{20,26,33,45,56,57,82}, prompted investigation into and development of various augmentation devices to improve the long-term outcome of spinal arthrodesis.

	Technology of Interbody Fusion Cages

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 

History
Bagby² was responsible for the early development of the lumbar interbody fusion cage. Working with a veterinarian, Grant, and a series of thoroughbred horses that had wobbler syndrome (a form of spondylitic myelopathy that leads to ataxia), he found that the Cloward technique²⁰, which requires obtaining bone from the iliac crest, resulted in unacceptable morbidity. Bagby then developed a novel device, the first interbody stainless-steel basket (the Bagby basket), which was a thirty-millimeter-long, twenty-five-millimeter-diameter cylinder that had two-millimeter fenestrations in its walls to allow bone ingrowth. During a standard anterior cervical decompression and reaming procedure, cancellous-bone chips were removed from the posterior aspects of the cervical vertebrae. These chips then were packed inside the basket to promote anterior interbody cervical fusion.

Subsequent studies revealed that horses treated with the Bagby technique had improved neurological function; some not only survived for many years but also won races³⁸. Other investigators began making modifications of this technique, including threads in the basket^72,108, adaptation of the cage for use in posterior lumbar interbody arthrodesis, and increases in the pullout and compressive strength⁷²; a two-cage technique also was developed, in 1988²⁵. In another study of horses, DeBowes et al.³⁰ compared the results of arthrodesis with use of bovine xenograft with those of arthrodesis with use of autogenous graft inside a Bagby basket; they found that the rate of fusion was better when the Bagby basket had been used and that this device did not collapse. After the arthrodesis, the gross appearance of the bovine xenograft was usually pale, and seven of eight sites that were investigated were composed of fibrous tissue. The autogenous graft and the Bagby basket contained little or no fibrous tissue. Maceration studies, with use of maggots to decompose the soft-tissue component, indicated that only two of eight bovine xenografts contained enough ossified tissue in the intervertebral space in order to hold the vertebrae together, whereas seven of eight autogenous grafts in the Bagby baskets contained enough tissue.

Current Types of Fusion Cages
A variety of cages are currently available, each with its own indications, advantages, and disadvantages. This review will focus on five devices: the Bagby-and-Kuslich device⁵¹ (BAK; Sulzer Spine-Tech, Minneapolis, Minnesota), the threaded interbody fusion device (TIBFD; Medtronic Sofamor-Danek Group, Memphis, Tennessee), the Ray cage (U.S. Surgical, Norwalk, Connecticut), the Harms titanium-mesh cage (DePuy-AcroMed, Cleveland, Ohio), and the Brantigan rectangular and rounded cages (DePuy-AcroMed). Most of these devices have been approved only for limited, investigational applications in humans because the long-term effects are not yet known. Thus, the BAK device may be used only for posterior, anterior, or lateral laparoscopic procedures; the TIBFD device, only in Food and Drug Administration-Investigational Device Exemption studies; the Ray cage, only as a posterior device; and the Brantigan cages, only as posterior devices and only in conjunction with posterior pedicle-screw instrumentation. Only the Harms cage has been approved for widespread, unrestricted use to date.

Mechanical, Biological, and Physiological Roles of Fusion Cages
In an effort to establish a baseline for the comparison of investigations of the role of fusion cages, Dennis et al.³¹ studied thirty-one patients who had had an anterior interbody arthrodesis at a total of forty levels with use of autogenous graft or allograft but not metal cages. The height of the disc space was measured in each patient preoperatively, early postoperatively, and at an average of twenty-nine months postoperatively. Although immediate postoperative radiographs showed an average increase in the disc-space height of 9.5 millimeters (89 percent), use of graft alone did not provide long-term distraction of the disc space or increased neuroforaminal height. At the time of the latest follow-up examination, the disc-space height had decreased in every patient; at nineteen of the forty vertebral levels, the height at the most recent examination was less than the preoperative height. That study demonstrated that autogenous graft or allograft alone cannot maintain neuroforaminal distraction. Maintaining this distraction is important because it promotes anterior load-sharing, increases the amount of space for the nerve roots, and prevents flatback syndrome.

Mechanical Role
Rapoff et al.⁷⁶ compared the mechanical effects of the TIBFD and BAK cages in six fresh-frozen, thawed spines from human cadavera and found that the insertional torque and maximum pushout loads were similar for the two cages. Other authors have determined that the amount of interspace distraction is as important to the overall stability of the construct as the individual characteristics of the fusion cage^{15,36,37,87,99}.

Kanayama et al.⁴⁷ used bench-top mechanical tests to assess different types of fusion cages in sixty functional calf-spine units, each consisting of one vertebral disc space and the adjacent vertebrae (Fig. 1-A). There were six specimens in each treatment group. The methods of preparation of the cage, anterior discectomy, and annular distraction with use of sized distraction plugs before insertion of the cage were similar for all ten constructs. The devices that were tested included two BAK cages, two BAK proximity cages, two Ray cages, two TIBFD cages, one Harms titanium-mesh cage, two Harms vertical titanium-mesh cages, two Brantigan rectangular carbon-fiber cages, a larger rounded Brantigan anterior lumbar interbody fusion cage shaped to fit within the interbody disc space, one femoral ring allograft, and two bone-dowel allografts. The modes of testing included axial compression (500 newtons), torsion (three newton-meters), flexion (five newton-meters), and lateral bending (five newton-meters). Intracage pressures were measured with pressure-needle transducers throughout the various loading conditions after a silicone elastomer gel had been injected into the cages and allowed to polymerize. The purpose of the gel was to provide a homogeneous material, simulating bone graft, inside each cage for measurement of strain. Pilot studies had shown that it was not useful to measure the strain on actual bone graft as such strain proved to be extremely variable and depended on the amount of force used to pack the bone graft inside the cage. With the numbers available for study, no significant differences were detected among the ten cage constructs with regard to functional stability (p > 0.05, one-way analysis of variance). Intracage pressure was not found to be significantly different among the Harms titanium-mesh vertical cages, the Brantigan cages, the femoral ring allograft, or the bone-dowel allografts; however, the four threaded cages (the BAK, BAK proximity, Ray, and TIBFD devices) had significantly lower intracage pressures than did the other implants (p < 0.05, one-way analysis of variance) (Fig. 1-B). These findings were supported by those of Oxland et al.⁷³, who found no difference in bench-top mechanical loading between two porous bilateral BAK implants and a central contoured SynCage implant with end-plate fit.

View larger version (154K): [in this window] [in a new window]   Fig. 1-A Photograph showing some of the devices studied by Kanayama et al.47, who used silicone elastomer gel inside cages to measure intracage pressures under in vitro loading conditions in an investigation of the forces acting on bone graft within different cage geometries. Bottom left, Brantigan cage; top left, Harms vertical cage; center, elastomer gel; top right, threaded femoral bone dowel; and bottom right, BAK cage.

View larger version (49K): [in this window] [in a new window]   Fig. 1-B Bar graph showing the intracage pressure measurements for the ten cage constructs. The four threaded titanium designs (BAK [Bagby and Kuslich], BAK proximity, Ray, and TIBFD [threaded interbody fusion device]) had significantly lower (more favorable) intracage pressures than did the other implants (p < 0.05, one-way analysis of variance). * = cage alone was significantly different from Group-A devices, ^ = cage alone was significantly different from BAK and TIBFD devices (F = 8.15, p < 0.001), and ^^ = cage alone was significantly different from cage with pedicle screws (p < 0.05). One pound per square inch = 6.89 kilopascals.

Biological Role
To date, to the best of my knowledge, the only study of long-term results with use of fusion cages was reported by Cunningham et al.²⁷. After an average of fourteen years (range, eight to fifteen years), histological analysis of six vertebral specimens from horses that had had an anterior interbody arthrodesis with insertion of a stainless-steel Bagby basket revealed successful fusion with mature trabecular bone spanning the sites of the arthrodesis. There was a significant decrease in bone-mineral density (p < 0.05) at the fusion site compared with that of the adjacent vertebral bodies, but this stress-shielding had no adverse clinical consequences. Sagittal microradiographs showed complete remodeling of the entire disc space, including the end plate and residual posterior remnants of the interbody disc posterior to the basket (Figs. 2-A and 2-B). Whether this equine model can be equated with the human situation remains to be determined.

View larger version (109K): [in this window] [in a new window]   Fig. 2-A Microradiographs showing the extent of trabecular remodeling fourteen years after treatment with a Bagby basket (Fig. 2-A) and a bone-dowel allograft (Fig. 2-B, arrows) from the study by Cunningham et al.27, who examined six equine specimens at an average of fourteen years after a successful anterior interbody arthrodesis and insertion of a Bagby stainless-steel basket.

View larger version (106K): [in this window] [in a new window]   Fig. 2-B Microradiographs showing the extent of trabecular remodeling fourteen years after treatment with a Bagby basket (Fig. 2-A) and a bone-dowel allograft (Fig. 2-B, arrows) from the study by Cunningham et al.27, who examined six equine specimens at an average of fourteen years after a successful anterior interbody arthrodesis and insertion of a Bagby stainless-steel basket.

Physiological Role
In a study of nine fresh-frozen lumbar spines from the cadavera of individuals who had had neuroforaminal stenosis, Chen et al.¹⁸ found that placement of silicone molds in the neuroforamina after the application of a fusion cage significantly increased the neuroforaminal volume (by 23 percent at the fourth and fifth lumbar level and by 22 percent at the fifth lumbar and first sacral level) and the posterior disc height (by 37 percent at the fourth and fifth lumbar level and by 45 percent at the fifth lumbar and first sacral level) (p < 0.001 for both).

	Selection of Patients for Arthrodesis with Use of an Interbody Fusion Cage

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
Ray⁷⁸, in a Food and Drug Administration-approved Investigational Device Exemption study, selected patients for insertion of a lumbar interbody fusion cage with use of six criteria: severe, disabling, intractable back pain; degenerated disc spaces with resultant pain; an absence of disc-space or systemic infection; no previous interbody arthrodesis at the target levels; an absence of degeneration at adjacent, neighboring disc spaces, whether or not they were painful; and no or Meyerding⁶⁹ grade-I spondylolisthesis. In addition, the disabling back pain had to have been present for at least one year and refractory to extensive nonoperative care and there had to be substantial loss of both disc height and mobility. Patients who had a disc-space height of more than twelve millimeters were excluded.

I believe that most of these criteria are not selective enough; cages have been used for patients who have general disc pain or disc spaces that appear dark on magnetic resonance imaging studies (so-called black-disc disease—that is, the earliest changes, on magnetic resonance images, caused by degenerative disc disease that is due to loss of hydration signal within the nucleus pulposus). I prefer a more conservative selection process, with use of cages limited to patients who have postlaminectomy syndrome or disc-space collapse with neuroforaminal narrowing. I do not use cages for patients who have black-disc disease or simply a positive discogram. Most patients whom I manage with a cage have disease involving only one disc level, and I do not use the device for those with involvement of more than two levels. If a patient has instability at more than two levels, it should be treated with a posterior approach and pedicle-screw instrumentation.

	Definition of Fusion

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
As stated in one review article³³, the rate of fusion "depends to a great extent on the investigator's interpretation." Because there is no single definition of what constitutes fusion, it is difficult if not impossible to compare the results of different studies. Moreover, it is difficult to determine radiographically if fusion has occurred. In addition, findings of biomechanical tests of stability do not always directly correspond to radiographic evidence of fusion. For example, a radiographically solid fusion with continuously bridging trabecular bone in a canine specimen (Fig. 3-A) had less mechanical stiffness than did a specimen that contained a two-to-three-millimeter-wide fibrous interface between the vertebral bodies (Fig. 3-B).

Fig. 3-A Radiographs demonstrating the paradox regarding a solid fusion compared with a so-called functional arthrodesis. Most investigators would agree that Fig. 3-A shows a fusion (as indicated by solid, continuous trabecular bone-bridging between the vertebrae) and that Fig. 3-B shows a pseudarthrosis according to the criteria of Stauffer and Coventry96 (a two-to-three-millimeter fibrous interface between the vertebral bodies). In laboratory testing, however, the flexural, torsional, and axial compressive stiffnesses were greater for the specimen shown in Fig. 3-B than for that shown in Fig. 3-A59; this was because the cross-sectional area of the hypertrophic pseudarthrosis callus in the specimen shown in Fig. 3-B was much greater than the cross-sectional area of the specimen shown in Fig. 3-A. (Reprinted, with permission, from: McAfee, P. C.; Regan, J. J.; Farey, I. D.; Gurr, K. R.; and Warden, K. E.: The biomechanical and histomorphometric properties of anterior lumbar fusions: a canine model. J. Spinal Disord., 1: 105, 1988.)

Fig. 3-B Radiographs demonstrating the paradox regarding a solid fusion compared with a so-called functional arthrodesis. Most investigators would agree that Fig. 3-A shows a fusion (as indicated by solid, continuous trabecular bone-bridging between the vertebrae) and that Fig. 3-B shows a pseudarthrosis according to the criteria of Stauffer and Coventry96 (a two-to-three-millimeter fibrous interface between the vertebral bodies). In laboratory testing, however, the flexural, torsional, and axial compressive stiffnesses were greater for the specimen shown in Fig. 3-B than for that shown in Fig. 3-A59; this was because the cross-sectional area of the hypertrophic pseudarthrosis callus in the specimen shown in Fig. 3-B was much greater than the cross-sectional area of the specimen shown in Fig. 3-A. (Reprinted, with permission, from: McAfee, P. C.; Regan, J. J.; Farey, I. D.; Gurr, K. R.; and Warden, K. E.: The biomechanical and histomorphometric properties of anterior lumbar fusions: a canine model. J. Spinal Disord., 1: 105, 1988.)

My criterion for fusion is the presence of bridging trabecular bone between the vertebral bodies. The most reliable radiographic indication of fusion postoperatively is the sentinel sign, or the presence of bridging bone anterior to the fusion cage (Figs. 4-A, 4-B, and 4-C). Similar to the late-maturation phases of callus formation in a fracture of the femur, the cross-sectional area of an exuberant fracture callus can restore normal stability before mature haversian bone is seen in radiographic continuity. One drawback of a fusion cage inserted after a so-called reamed-channel discectomy is that the reparative process is confined to a smaller cross-sectional area (the fenestrations in the cage) in contrast to uninhibited hypertrophy.

View larger version (100K): [in this window] [in a new window]   Figs. 4-A, 4-B, and 4-C: It is often difficult to confirm a lumbar fusion with use of flexion and extension radiographs alone. The most reliable criterion of a successful fusion in association with a fusion cage is the presence of trabecular bone-bridging in continuity between vertebrae. Fig. 4-A: Lateral radiograph made six months after an anterior laparoscopic arthrodesis of the fifth lumbar to the first sacral vertebra for the treatment of postlaminectomy instability. Additional iliac-crest bone graft was packed anterior to the BAK fusion cage (arrows).

View larger version (97K): [in this window] [in a new window]   Fig. 4-B Illustration (Fig. 4-B) showing the principle of ream long-cage short66, which ensures that additional cancellous bone (Fig. 4-C, arrows) can be visualized anterior to the cage. This is an example of the so-called sentinel sign, which indicates a successful arthrodesis.

View larger version (117K): [in this window] [in a new window]   Fig. 4-C Illustration (Fig. 4-B) showing the principle of ream long-cage short66, which ensures that additional cancellous bone (Fig. 4-C, arrows) can be visualized anterior to the cage. This is an example of the so-called sentinel sign, which indicates a successful arthrodesis.

The interpretation of fusion on the basis of radiographs is also subject to controversy. Stauffer and Coventry⁹⁶ defined fusion as bridging and no motion. However, in recent studies of BAK cages, fusion was considered to have occurred even in the presence of as much as 5 degrees of difference (motion) between flexion and extension radiographs^1,51,108. Some authors have thought that more than 5 degrees of motion as seen on lateral flexion and extension radiographs indicates a failure of fusion^11,13,14,78. Others have defined fusion with use of stricter criteria (only 2 or 3 degrees of motion as seen on flexion and extension radiographs)^34,53,57,58. Still others have stated that radiolucent areas that are wider than two millimeters and extend along at least 50 percent of the bone adjacent to the implant are indicative of failure^40,108.

Deciding whether a patient has a fusion or a failure of the arthrodesis on the basis of the amount of motion seen on flexion and extension radiographs is difficult for several reasons. First, the difference in the range of motion among asymptomatic individuals can range from 7 to 14 degrees¹³, so it may not be accurate to use a particular degree of motion as the baseline with which to determine the presence of fusion. Second, radiographs may not accurately depict the range of motion that is possible because a patient who has pain on bending may bend less than he or she can. Third, the measurement of angular motion may be unreliable in the presence of pedicle-screw instrumentation, which may decrease motion even in patients who have a pseudarthrosis and thus result in a false-positive finding of fusion. The effect, on the findings on stress radiographs, of anterior cage instrumentation alone in the absence of a fusion has not been studied, to my knowledge⁵².

My colleagues and I⁶⁶ reported on twenty patients who had had additional spinal reconstruction procedures after failure of an arthrodesis with use of a cage. Five of these patients had been thought, by their referring surgeons, to have had a solid fusion on the basis of flexion and extension radiographs made less than two years postoperatively; however, on follow-up more than two years after the operation, all five were found to have gross motion, subsidence, mechanical pain, and migration of the cage. Late pseudarthrosis and instability also had developed. Thus, that study demonstrated the unreliability of assessment of fusion on the basis of flexion and extension radiographs alone. Because of the unreliability of radiographic interpretation of motion, I prefer to define fusion as simply the presence of bridging trabecular bone between vertebral bodies.

In a study of forty-nine patients who had had exploration of the fusion mass during removal of the hardware, Blumenthal and Gill⁴ found only 69 percent agreement between the radiographic and operative findings; 90 percent of the patients had a successful fusion. Those authors suggested that, in one of five patients, plain radiographs had led to an underestimation of the degree of fusion and the premineralized osteoid might have been functionally fused while appearing radiolucent on radiographs.

Brantigan et al.¹³ used the most stringent criteria for fusion, especially considering that the Brantigan cage for posterior lumbar interbody arthrodesis is radiolucent, allowing better radiographic visualization of the dynamics of the bone graft than do cages composed of titanium, which creates artifacts. According to those authors, no motion was acceptable, but it must be remembered that the devices always were used in conjunction with pedicle screws.

In a prospective, multicenter clinical trial, Yuan et al.¹⁰⁸ used the following definition of fusion to study the BAK cage in a Food and Drug Administration-approved Investigational Device Exemption study reported by Alpert¹ (PMA [Premarket Approval] P950002). The fusion was considered to be solid if there were no dramatically obvious radiolucencies and there was less than 5 degrees of vertebral motion in the sagittal plane as assessed with digitization methods. All radiographs that demonstrated between 3 and 7 degrees of sagittal motion were evaluated by an independent radiologist. Patients who had had a two-level procedure were considered to have a successful fusion only if both levels were fused (see Results of Clinical Series).

In an Investigational Device Exemption study of titanium fusion cages, Ray⁷⁸ defined fusion according to six criteria: (1) lack of any visible motion, or less than 3 degrees of intersegmental change, as seen on flexion and extension radiographs; (2) lack of a dark halo around the implant; (3) minimum loss of disc-space height, indicating a resistance to collapse of the cancellous vertebral bone; (4) lack of visible fracture of the device, graft, or vertebrae; (5) lack of substantial sclerotic changes in the recipient bone bed or the graft; and (6) visible bone within the hollow Ray titanium fusion cage as seen on anterior, posterior, or Ferguson radiographs³². If the radiologist determined that the vertebral bodies were fused but the surgeon thought that they were not, fusion was considered not to have occurred (see Results of Clinical Series).

	Hybrid Interbody Grafts: Biological Cages

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
Although he was not the first author of the published study, O'Brien is credited with the concept of the so-called hybrid interbody graft, a biological fusion cage consisting of a femoral cortical allograft ring packed with autogenous cancellous bone graft⁴⁴. Of forty patients who were managed with this technique, thirty-two had posterior instrumentation and eight did not. The overall rate of fusion was seventy (96 percent) of seventy-three levels. The average interbody disc height increased postoperatively but returned to preoperative values at an average of 1.4 years (range, 1.0 to 2.4 years).

Because it is composed entirely of bone, the hybrid cage is capable of complete remodeling, unlike titanium cages. Additionally, it can be used in patients who have an infection (Figs. 5-A, 5-B, 5-C, 5-D, 5-E, 5-F and 5-G). The femoral allograft portion of the cage determines the acute or immediate stability of the construct, whereas the autogenous iliac-crest graft determines the long-term stability.

View larger version (104K): [in this window] [in a new window]   Figs. 5-A through 5-G: Magnetic resonance images and radiographs of a thirty-five-year-old man who was managed with a biological (hybrid) threaded femoral bone-dowel allograft packed with autogenous iliac-crest bone graft. Fig. 5-A: Magnetic resonance image made just before a posterior laminectomy and discectomy at the fifth lumbar and first sacral levels for the treatment of a central disc herniation (arrowhead).

View larger version (103K): [in this window] [in a new window]   Fig. 5-B: Magnetic resonance image made within one month after the operation, showing pyogenic vertebral osteomyelitis.

View larger version (100K): [in this window] [in a new window]   Fig. 5-C Radiograph made after six weeks of intravenous administration of antibiotics. The infection resolved, but the patient remained extremely symptomatic, with mechanical back pain and erosion (arrowheads) of the vertebral end plate.

View larger version (108K): [in this window] [in a new window]   Fig. 5-D Anteroposterior and lateral radiographs made three months after treatment with a threaded femoral cortical bone-dowel allograft, demonstrating restoration of interbody and posterior neuroforaminal height.

View larger version (114K): [in this window] [in a new window]   Fig. 5-E Anteroposterior and lateral radiographs made three months after treatment with a threaded femoral cortical bone-dowel allograft, demonstrating restoration of interbody and posterior neuroforaminal height.

View larger version (122K): [in this window] [in a new window]   Fig. 5-F Anteroposterior and lateral radiographs made two years postoperatively, demonstrating the extent of remodeling possible with use of a threaded femoral bone-dowel allograft. The back pain, which occurred with spinal motion, had resolved completely, and the patient had returned to work on a full-time basis with no recurrence of the infection.

View larger version (116K): [in this window] [in a new window]   Fig. 5-G Anteroposterior and lateral radiographs made two years postoperatively, demonstrating the extent of remodeling possible with use of a threaded femoral bone-dowel allograft. The back pain, which occurred with spinal motion, had resolved completely, and the patient had returned to work on a full-time basis with no recurrence of the infection.

	Results of Clinical Series

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 

BAK Investigational Device Exemption Study
Yuan et al.¹⁰⁸, Kuslich et al.⁵¹, and Alpert¹ reported on a large clinical series of 947 patients in a prospective, multicenter trial of the BAK device. An anterior approach was used in 591 operations (62 percent), and a posterior approach was used in 356 (38 percent). One hundred and fourteen patients (12 percent) had spondylolisthesis. The average duration of the symptoms before the operation was 5.5 years (minimum, six months); 767 patients (81 percent) had had the symptoms for more than one year. Two hundred and forty-six patients (26 percent) were smokers, and 341 (36 percent) had had previous spinal procedures, primarily decompressions.

Pain was quantified with use of a 6-point analog scale similar to that proposed by Prolo et al.⁷⁵, with 1 point indicating no pain and 6 points, disabling pain. The average preoperative pain score was 5.0 points (marked pain); 729 patients (77 percent) reported marked or disabling pain. The average pain score twelve months postoperatively was 3.1 points (mild pain), and that at twenty-four months was 2.9 points. Twenty-four months after the operation, 805 patients (85 percent) reported a decrease in pain.

The functional outcome was evaluated, with use of a numerical scale, according to seven parameters: the ability to stand, sit, walk, squat, and put on socks and shoes; the level of recreational activity; and the level of work. The best (lowest) possible score was 7 points, and the worst (highest) score was 32 points. (An asymptomatic, or so-called normal, individual would score between 9 and 12 points on this scale.) The average functional score was 20.9 points preoperatively, 15.2 points at twelve months, and 14.4 points at twenty-four months.

Yuan et al.¹⁰⁸ also followed the patients with regard to their ability to return to work postoperatively. At the time of the operation, only 341 (36 percent) of the 947 patients were working outside the home; 502 (53 percent) were not working because of disability, and 104 (11 percent) were homemakers, students, or retirees. Eight hundred and forty-three patients were considered to be eligible for work after the operation; these included patients who either had worked or had been receiving disability compensation before the operation. Five hundred and seventy-three (68 percent) of these patients returned to work at twelve months, and 658 (78 percent) returned at twenty-four months. Of 283 patients who were seen for a two-year follow-up evaluation, 91 percent had fusion (defined as the absence of substantial radiolucencies and less than 5 degrees of vertebral motion in the sagittal plane as assessed with digitization methods)¹.

To gain perspective on the rates of fusion associated with lumbar interbody fusion cages, it is helpful to review the prospective study reported by Zdeblick¹¹⁰ in 1993. One hundred and twenty-four patients were randomly assigned to one of three treatment groups: posterolateral arthrodesis with use of autogenous bone grafts (group I), posterolateral arthrodesis supplemented with semirigid pedicle-screw instrumentation (group II), or posterolateral arthrodesis with autogenous grafts and rigid pedicle-screw-and-rod fixation (group III). The overall rate of fusion was 65 percent for group I, 77 percent for group II, and 95 percent for group III.

Ray Titanium Fusion Cage
The Investigational Device Exemption study of the Ray cage⁷⁸ comprised 211 patients who were followed for a minimum of twenty-four months postoperatively. The indications for the procedure were severe, disabling back pain (203 patients; 96 percent); major annular degeneration (156 patients; 74 percent); disc herniation (120 patients; 57 percent); a decrease in the height of the disc space of more than 10 percent (ninety-one patients; 43 percent); and formation of osteophytes (forty-four patients; 21 percent). Ninety-five patients (45 percent) had had previous operations on the spine but not arthrodesis. At the time of follow-up, 203 patients (96 percent) had radiographic evidence of fusion, defined as an absence of motion as seen on flexion and extension radiographs with use of a radiographic overlay method⁴⁵, an absence of a radiographically apparent dark halo around the cage, and the continued presence of visible bone within the cage as seen on a Ferguson radiograph³². The clinical outcome, according to the socioeconomic and functional improvement scale described by Prolo et al.⁷⁵, was excellent for eighty-four patients (40 percent), good for fifty-three (25 percent), fair for forty-four (21 percent), and poor for thirty (14 percent).

Investigational Device Exemption Study by Brantigan et al.¹³
Brantigan et al.¹³ meticulously defined clinical success with use of parameters derived from the scale of Prolo et al.⁷⁵ (Table I). The scores for pain, function, work status, and use of medication (all determined on a 5-point scale) were combined, yielding a possible overall score of 4 to 20 points, with 17 to 20 points indicating an excellent result; 13 to 16 points, a good result; 9 to 12 points, a fair result; and 4 to 8 points, a poor result. The result was considered a clinical success if the two-year rating was excellent or good, and it was considered fair if the score improved 3 points or more compared with the preoperative score.

Harms Vertical Titanium-Mesh Cage
A vertically upright titanium-mesh cage was developed by Harms et al.^41,42, and the cage has been in widespread clinical use since 1991. The risk of complications is similar to that associated with the Brantigan cage because it is used in conjunction with posterior pedicle-screw instrumentation. The device is different from horizontal cages because it can be cut to the desired intradiscal dimensions intraoperatively with use of a wire-cutter. Harms developed the concept of this device to provide anterior load-sharing support for corpectomy defects created after anterior decompression for the treatment of fractures and tumors. In order to avoid entering the spinal canal, Harms et al.⁴² used an anterior interbody approach combined with a posterior approach for placement of instrumentation in twenty-nine patients who had grade-I or II spondylolisthesis. In eighty-three patients who had a higher grade (III, IV, or V) of spondylolisthesis (a greater degree of slippage), they performed posterior reduction and stabilization with use of a posterior lumbar interbody arthrodesis and insertion of a cage packed with autogenous bone chips. The triangular tines on the edges of the cage were designed to dig into the vertebral end plates to prevent recurrence of lumbosacral spondylolisthesis by resisting the shear forces at the disc space between the fifth lumbar and first sacral vertebral bodies.

Despite its widespread use, there have been no multicenter prospective or Investigational Device Exemption studies of the Harms cage, to my knowledge.

	Economic Comparison

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
In a 1997 prospective, nonrandomized study of patients who had severe, disabling back pain and disc degeneration, twenty-five patients were managed with a Ray threaded fusion cage and twenty-five had a combined anterior and posterior arthrodesis (the 360-degree technique) with pedicle-screw instrumentation⁷⁷. The average combined cost (for the surgeon, hospital, and anesthesiologist) of the one-level procedures performed with use of the Ray cage was $25,171 and that for the 360-degree procedures was $41,813—a difference of $16,642 (40 percent). In addition, ten patients who had had the 360-degree arthrodesis later had removal of the pedicle-screw instrumentation, which added $8635 to the cost for each patient. The final average cost of the 360-degree procedures was $22,889 higher than that of the corresponding procedures performed with use of the Ray cage.

	Complications

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
Several studies have confirmed that complications associated with interbody fusion cages are due not to failure of the hardware but rather to the operative approach (anterior, posterior, or endoscopic)^51,64,81,108. Penta et al.⁷⁴ studied fifty-two patients with use of magnetic resonance imaging ten years after an anterior lumbar interbody arthrodesis that had not included insertion of a fusion cage in order to determine if the arthrodesis increased the rate of disc degeneration at spinal levels adjacent to the level of fusion. They found normal adjacent discs associated with a solid fusion to the sacrum in 67 percent (thirty-five) of the patients and concluded that the procedure does not cause degenerative changes in adjacent discs.

Shirado et al.⁹¹ found that posterior lumbar interbody arthrodesis with use of tricortical grafts decreased the flexion-extension and torsional stiffness in the acute postoperative period.

Wetzel and LaRocca¹⁰³ studied twelve patients who had had failure of a posterior lumbar interbody arthrodesis. All twelve had chronic radiculopathy due to extensive epineural and endoneural fibrosis "provoked by extensive epidural manipulation required" during the procedure. Those authors believed that there was also a mechanical shortcoming inherent in the procedure because adjacent unfused segments became symptomatic in four patients.

Glassman et al.³⁵ reported that a complication was more likely to occur when the cage was inserted through a posterior rather than an anterior approach. Trapezoidal titanium cages that initially were inserted during a posterior arthrodesis, even in the presence of posterior pedicle-screw instrumentation, retropulsed into the spinal canal, causing neurological symptoms and weakness of the lower extremities. These patients subsequently had removal of the cage and placement of a femoral ring allograft packed with autogenous cancellous bone graft.

Ray Cage and BAK Device
The types and rates of complications in most series of fusion cages have been approach-specific, with very similar complications reported in patients managed with the same device^51,78,108. There have been essentially no reported cases of fracture of titanium cages, whereas there has been a fairly substantial rate of pedicle-screw breakage (range, 0.9 percent [eighteen of 1999] to 27 percent [thirty-three of 124]^{36,37,52,53,97}). In one report⁵¹, the rate of reoperation for patients who had a fusion cage was 4 percent (forty-two of 947) and reoperation was most common in the first 100 days because of migration of the cage, a technical complication secondary to inadequate interbody distraction before reaming and tapping. Dural tears (reported prevalence, 10.1 percent of 356 patients¹⁰⁸) have been related exclusively to the posterior approach, whereas retrograde ejaculation, damage to major vessels, urological complications, and postoperative ileus (reported prevalences, 1.9, 1.7, 1.4, and 2.2 percent, respectively, of 591 patients¹⁰⁸) have been associated with the anterior retroperitoneal approach. In 1997, Hacker⁴⁰ reported on a patient who had had operative exploration because of a compressive radiculopathy that had developed after a posterior lumbar interbody arthrodesis with use of a BAK cage. He noted that a laterally positioned implant had resulted in foraminal nerve-root encroachment.

Brantigan Internal Fixation Cage
Most of the complications in the Investigational Device Exemption study of the Brantigan internal fixation cage were due not to the cage but rather to the posterior pedicle-screw instrumentation¹³. Of 219 patients, seventy-eight (36 percent) had removal of the pedicle screws, thirty (14 percent) had device-related complications (all but two of which were related to the pedicle screws), and eighteen (8 percent) had a revision operation.

Laparoscopic Insertion of Fusion Cages
Regan et al.^79-81 conducted the most comprehensive study comparing, with regard to efficacy and the prevalence of complications, open and laparoscopic insertion of fusion cages. Two hundred and fifty consecutive patients who had had a laparoscopic arthrodesis at the fourth and fifth lumbar or the fifth lumbar and first sacral levels with insertion of a BAK device were enrolled in a prospective, multicenter study between April 1992 and December 1996. These patients were compared with a cohort of 591 patients who had had an open anterior arthrodesis with insertion of a BAK device between April 1992 and November 1995, performed by forty-two surgeons at nineteen medical centers in the United States. The indications for the operation were the same in both groups, and the operative approach depended on the surgeon's preference. Forty percent of the patients in both groups had had a previous laminectomy. Three hundred and five patients who had had a one-level open procedure and 215 who had had a one-level laparoscopic procedure were similar with regard to the average age, gender, diagnostic subgroups, and preoperative duration of pain (Table II). The patients who had had a laparoscopic procedure at the fourth and fifth lumbar levels had, on the average, a significantly longer operative time (p < 0.001) but significantly less intraoperative blood loss (p = 0.023) and a significantly shorter stay in the hospital (p = 0.003) than did those who had been managed with an open procedure (Table III). The only perioperative complications specific to the laparoscopic procedures were six instances of iatrogenic disc herniation due to placement of the reamers, taps, or fusion cages too far laterally, which caused compression of a nerve root in the lateral recess (Table IV). Regan et al.^79-81 stated that, after the first five to ten procedures, the level of operative skill had advanced to the point that the laparoscopic procedure was as safe and effective as the open anterior approach; it also had the advantage of necessitating one day less of hospitalization.

In an effort to avoid vascular complications and dissection of major vessels, some authors^65,79 have recommended that anterior interbody arthrodesis be performed with the patient in the lateral decubitus position and that the cage or bone graft be inserted in a transverse direction. This approach can be used from the first to fifth lumbar levels, but it is not usually possible at the fifth lumbar and first sacral levels. Mayer⁶⁸ performed a microsurgical arthrodesis in twenty-five patients at the second and third, third and fourth, or fourth and fifth lumbar levels, but all of the patients needed posterior stabilization with an internal fixator. My colleagues and I⁶⁵ performed an arthrodesis at the first through fifth lumbar levels with use of a minimally invasive anterior retroperitoneal approach and insertion of a longer BAK cage in a transverse or lateral direction (Figs. 6-A and 6-B). The average duration of hospitalization was 2.9 days (range, zero days [for outpatient procedures] to five days). The average estimated intraoperative blood loss was 205 milliliters (range, five to 1000 milliliters). No patient had migration or substantial subsidence of the implant or a pseudarthrosis at an average of 24.3 months (range, twelve to forty months) postoperatively. The lateral transverse insertion of the fusion cage obviated the need for dissection and mobilization of the common iliac veins and arteries. No patient needed supplemental posterior instrumentation after this approach.

View larger version (122K): [in this window] [in a new window]   Fig. 6-A Anteroposterior and lateral radiographs showing the extent of the fusion (arrows, Fig. 6-A) two years after an arthrodesis through a minimally invasive retroperitoneal approach that allowed two larger fusion cages to be inserted in a lateral direction between the third and fourth lumbar levels65. In contrast to transperitoneal procedures, this procedure obviates the need for dissection and mobilization of the great vessels.

View larger version (95K): [in this window] [in a new window]   Fig. 6-B Anteroposterior and lateral radiographs showing the extent of the fusion (arrows, Fig. 6-A) two years after an arthrodesis through a minimally invasive retroperitoneal approach that allowed two larger fusion cages to be inserted in a lateral direction between the third and fourth lumbar levels65. In contrast to transperitoneal procedures, this procedure obviates the need for dissection and mobilization of the great vessels.

	Recent Developments: the Fusion Cage as a Vehicle for Delivery of Osteoinductive Materials

Top Introduction Background Technology of Interbody Fusion... Selection of Patients for... Definition of Fusion Hybrid Interbody Grafts:... Results of Clinical Series Economic Comparison Complications Recent Developments: the Fusion... Discussion References

 
Boden et al.^5-7 reported the histological and computed tomographic findings in five adult rhesus monkeys that had had laparoscopic exposure of the lumbosacral spine followed by insertion of a hollow titanium cylindrical cage filled with a collagen sponge soaked with recombinant bone morphogenetic protein-2 (Genetics Institute, Cambridge, Massachusetts). All five monkeys had a solid fusion as determined by manual palpation. The computed tomographic scans demonstrated fusion with continuous bone growth through the cage.

Cunningham et al.²⁹ performed a comprehensive endoscopic study in the thoracic spine of sheep to compare the use of a BAK cage filled with osteogenic protein-1 with that filled with autogenous iliac-crest bone graft. The criterion that those authors used to document a solid fusion was bridging of the trabecular network from end plate to end plate as seen in the cage on midsagittal microradiographs (Figs. 7-A, 7-B, and 7-C) ^{6,12,43,48,86,88,89,92,93,95,98,105,109}. Those authors evaluated the findings of biomechanical testing, computed tomography, microradiography, and quantitative histomorphometric measurements (the amount of fibrous and bone tissue within and surrounding the cage). Twelve sheep had a multilevel thoracic decompression with use of a thoracoscopic