Anterior Lumbar Interbody Arthrodesis Research Articles

Commentary: An evolving perception of the risk of rhBMP-2 use for anterior spinal interbody fusions

COMMENTARY ON: Carragee EJ, Mitsunaga KA, Hurwitz EL, Scuderi GJ. Retrograde ejaculation after anterior lumbar interbody fusion using rhBMP-2: a cohort controlled study. Spine J 2011;11:511–6 ( in this issue ).

Recombinant Human Bone Morphogenetic Protein-2 on an Absorbable Collagen Sponge with an Osteoconductive Bulking Agent in Posterolateral Arthrodesis with Instrumentation

Recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge has been shown to be a safe and effective replacement for iliac crest bone graft when used with a threaded fusion device in anterior lumbar interbody arthrodesis. Use of rhBMP-2 on an absorbable collagen sponge in posterolateral lumbar arthrodesis requires the addition of a bulking agent to provide resistance against compression and to serve as an osteoconductive scaffold for new bone formation. We performed a prospective, randomized, multicenter pilot study to investigate the use of rhBMP-2 on an absorbable collagen sponge combined with a ceramic-granule bulking agent as a replacement for autogenous iliac crest bone graft in single-level posterolateral lumbar arthrodesis with instrumentation. The investigational group (twenty-five patients) was treated with a 1.5 mg/mL solution of rhBMP-2 on two strips of absorbable collagen sponge (total dose of rhBMP-2, 12 mg) combined with 10 cm(3) of ceramic granules. The control group (twenty-one patients) received iliac crest bone graft. Clinical outcomes were assessed with use of well-established instruments. Radiographs were reviewed to assess consolidation of fusion. Eighty-eight percent (twenty-two) of the twenty-five patients in the investigational group and 86% (eighteen) of the twenty-one patients in the control group were considered to have completed the twenty-four-month follow-up. At all follow-up intervals, there were significant improvements in the clinical outcome measures, including the Oswestry Disability Index (ODI) scores, Short Form-36 scores, and back and leg pain scores, in both groups. At twenty-four months, the improvement in the mean ODI score, as compared with the preoperative score, was 28.2 points in the investigational group and 23.0 points in the control group. By twenty-four months, 95% (eighteen) of nineteen patients in the investigational group compared with 70% (fourteen) of twenty in the control group had a radiographically documented fusion. The overall success rate was 81% (seventeen of twenty-one) in the investigational group and 55% (eleven of twenty) in the control group (p = 0.345). Compared with an iliac crest bone graft, the combination of an absorbable collagen sponge soaked with rhBMP-2 and ceramic granules resulted in trends toward improvements in clinical outcomes and toward a higher rate of radiographic fusion. This combination of an osteoinductive agent with an osteoconductive matrix may be an effective replacement for autograft in single-level posterolateral lumbar arthrodeses with instrumentation.

Clinical and Radiographic Analysis of an Optimized rhBMP-2 Formulation as an Autograft Replacement in Posterolateral Lumbar Spine Arthrodesis

Previous studies have demonstrated the ability of recombinant human bone morphogenetic protein to achieve a solid fusion in anterior lumbar interbody arthrodesis. The purpose of this study was to compare iliac crest bone graft and recombinant human bone morphogenetic protein-2, combined with a carrier consisting of bovine collagen and beta-tricalcium phosphate-hydroxyapatite to create a compression-resistant matrix, for instrumented single-level posterolateral arthrodesis. Four hundred and sixty-three patients with symptomatic single-level lumbosacral degenerative disease with no greater than grade-1 spondylolisthesis were treated with single-level instrumented posterolateral arthrodesis through an open midline approach. Patients were randomly assigned to either the recombinant human bone morphogenetic protein-2 matrix group (239 patients) or the autogenous iliac crest bone-graft group (224 patients). The Oswestry Disability Index, Short Form-36, and back and leg pain scores were determined preoperatively and at 1.5, three, six, twelve, and twenty-four months postoperatively. Radiographs and computed tomography scans were made at six, twelve, and twenty-four months postoperatively to evaluate for fusion. The mean operative time and mean blood loss in the recombinant human bone morphogenetic protein-2 matrix group (2.5 hours and 343.1 mL, respectively) were significantly less than those in the iliac crest bone-graft group (2.9 hours and 448.6 mL). Both groups showed similar improvements in clinical outcomes and reduced pain. At twenty-four months, 60% of the iliac crest bone-graft group reported donor-site pain. At twenty-four months, fusion was evident in 96% of the patients in the recombinant human bone morphogenetic protein-2 matrix group compared with 89% in the iliac crest bone-graft group (p = 0.014). There was a significant difference (p = 0.011) in the rate of failures because of nonunion (eighteen patients with an iliac crest bone graft compared with six patients with the recombinant human bone morphogenetic protein-2 matrix). Also, the number of patients requiring second surgeries was significantly higher in the iliac crest bone-graft group (thirty-six patients) compared with the recombinant human bone morphogenetic protein-2 matrix group (twenty patients) (p = 0.015). The use of recombinant human bone morphogenetic protein-2 in instrumented posterolateral lumbar arthrodesis decreases operative time and blood loss and produces earlier and higher fusion rates than does iliac crest bone graft. Clinical outcomes are similar to those with iliac crest bone graft. Thus, the need for harvesting iliac crest bone is eliminated along with the morbidities associated with the harvest procedure.

Six-Year Outcomes of Anterior Lumbar Interbody Arthrodesis with Use of Interbody Fusion Cages and Recombinant Human Bone Morphogenetic Protein-2

Twenty-four-month outcomes have been reported for patients with degenerative lumbar disc disease who were treated with stand-alone anterior lumbar interbody arthrodesis with use of dual tapered interbody fusion cages and recombinant human bone morphogenetic protein-2. This report represents an update of the clinical and radiographic results of this treatment at six years. Two hundred and seventy-seven patients with single-level degenerative disc disease with up to grade-I spondylolisthesis were enrolled in two prospective, multicenter, U.S. Food and Drug Administration-approved investigational device exemption studies and were treated with an open or a laparoscopic surgical procedure. The patients received recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge with lumbar fusion cage implants. One hundred and forty-six patients completed the six-year clinical follow-up evaluations, and 130 patients had complete radiographic follow-up at six years. Outcomes were determined with use of well-established clinical outcome measurements (Oswestry Disability Index, Short Form-36, and back and leg pain scores) and radiographic assessments. At six years, 128 (98%) of the 130 patients treated with recombinant human bone morphogenetic protein-2 and stand-alone fusion cages had a fusion. The second surgery rate was 6.7% (eighteen patients) prior to two years and 3.7% (seven patients) from two to six years. A worst-case scenario analysis, which includes all second surgical procedures due to pseudarthrosis, resulted in a fusion rate at seventy-two months of 91% (128 of 141). Significant improvements in the Oswestry Disability Index scores, Short Form-36 health survey physical component summary scores, and back and leg pain scores were achieved by six weeks in both the open and laparoscopic groups and were sustained at six years (p < 0.001). The percentage of patients who were working at six months (63%) was higher than the percentage who had been working preoperatively (52%), and this improvement was sustained at six years (68%). The use of dual tapered threaded fusion cages and recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge obtained and maintained intervertebral spinal fusion, improved clinical outcomes, and reduced pain after anterior lumbar interbody arthrodesis in patients with degenerative lumbar disc disease.

The Effect of Platelet-Rich Plasma and Bone Marrow on Murine Posterolateral Lumbar Spine Arthrodesis with Bone Morphogenetic Protein

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has had limited success in stimulating osteogenesis at the site of posterolateral lumbar spine arthrodesis when used at the currently approved human dose for anterior lumbar interbody arthrodesis. The objective of the present study was to investigate the effect of co-administration of fresh harvested autologous bone marrow aspirate and platelet-rich plasma on rhBMP-2-mediated in vivo murine posterolateral lumbar spine arthrodesis. Forty adult male mice underwent posterolateral intertransverse process arthrodesis from L4 to L6. In three experimental groups, a collagen sponge was placed on each side, overlaying the decorticated transverse processes. Each collagen sponge was presoaked for fifteen minutes with 31 microg of rhBMP-2 in a 100-microL solution containing either saline solution (n = 10), platelet-rich plasma (n = 10), or donor bone-marrow cells (n = 10). Control mice underwent decortication alone (n = 10). The lumbar spine was harvested four weeks after surgery, and spinal fusion was evaluated on the basis of radiographs, computed tomography, and histological analysis. Control mice showed no evidence of spinal fusion. The rate of fusion was radiographically and histologically similar in all three experimental groups. The area, volume, and density of the fusion mass were significantly greater (p < 0.05) for the group treated with rhBMP-2 and bone marrow as compared with the group treated with rhBMP-2 alone. The group treated with rhBMP-2 and platelet-rich plasma had intermediate fusion area and density. Histologically, the spines treated with rhBMP-2 alone consistently showed the presence of cortical bone between the two transverse processes but fewer trabeculae within the fusion mass; bone marrow co-augmentation resulted in more trabeculae within the fusion mass and a thicker cortical perimeter. The present study quantitatively confirmed a synergistic effect of bone marrow cells when added to rhBMP-2 in an in vivo mouse posterolateral lumbar spine fusion model. The volume, area, and density of the fusion mass were significantly increased by augmentation with bone marrow cells.

Histological Analysis of a Displaced Femoral Ring Allograft Spacer Filled with a Recombinant Human Bone Morphogenetic Protein-2-Soaked Collagen Sponge: A Case Report

R ecombinant human bone morphogenetic protein-2 (rhBMP-2) has been tested as a bone-graft substitute in randomized, prospective clinical trials since 19971-4. In certain procedures, its efficacy with regard to both arthrodesis rates and clinical outcome has equaled that obtained with iliac crest bone graft. The United States Food and Drug Administration recently approved the use of rhBMP-2 as a bone-graft replacement during anterior lumbar interbody arthrodesis in conjunction with a tapered, threaded intervertebral cage (LT-CAGE; Medtronic Sofamor Danek, Minneapolis, Minnesota). Although the Food and Drug Administration has approved the use of rhBMP-2 only in conjunction with the LT-CAGE device, an off-label use of rhBMP-2 with structural allograft bone in anterior lumbar interbody arthrodesis has been reported. A pilot clinical trial in which allograft bone dowels and an rhBMP-2-soaked absorbable collagen sponge were used for lumbar interbody arthrodesis demonstrated favorable outcomes and good arthrodesis rates3. There have been some concerns about the potential up-regulation of osteoclastic activity leading to rapid resorption of the allograft when the allograft is used with rhBMP-2. Some of this concern originates from the fact that rhBMP-2 can stimulate differentiation and enhance survival of some populations of osteoclasts5. However, thus far, this concern has not been clearly validated in basic science or clinical investigations. In fact, rhBMP-2 has been used to enhance healing of allograft fractures in rats6 and to enhance the biomechanical properties of allograft-native bone interface in dogs7. We report a case in which a femoral ring spacer filled with an rhBMP-2-soaked sponge was retrieved from a woman who had undergone a combined anterior and posterior spinal reconstruction but had early dislodgment of the interbody graft. To our knowledge, this is the first report of retrieval and analysis of an rhBMP-2-soaked collagen sponge in …

Use of rhBMP-2 in Combination with Structural Cortical Allografts: Clinical and Radiographic Outcomes in Anterior Lumbar Spinal Surgery

Recombinant human bone morphogenetic protein-2 soaked into an absorbable collagen sponge (rhBMP-2/ACS) has been shown in a nonhuman primate study and in a pilot study in humans to promote new bone formation and incorporation of an allograft device when implanted in patients undergoing anterior lumbar interbody arthrodesis. However, a larger series with longer follow-up is needed to demonstrate its superiority to autogenous iliac crest bone graft. Between 1998 and 2001, a two-part, prospective, randomized, multicenter study of 131 patients was conducted to determine the safety and efficacy of the use of rhBMP-2/ACS as a replacement for autogenous iliac crest bone graft in anterior lumbar spinal arthrodesis with threaded cortical allograft dowels. Patients were randomly assigned to a study group that received rhBMP-2/ACS or to a control group that received autograft. The clinical and radiographic outcomes were determined with use of well-established instruments and radiographic assessments. The patients in the study group had significantly better outcomes than the control group with regard to the average length of surgery (p < 0.001), blood loss (p < 0.001), and hospital stay (p = 0.020). Fusion rates were significantly better in the study group (p < 0.001). The average Oswestry Disability Index scores, Short-Form-36 physical component summary scores, and low-back and leg-pain scores were significantly better in the study group (p < 0.05). In patients undergoing anterior lumbar interbody arthrodesis with threaded allograft cortical bone dowels, rhBMP-2/ACS was an effective replacement for autogenous bone graft and eliminated the morbidity associated with graft harvesting.

An Investigational Study on the Healing Process of Anterior Spinal Arthrodesis Using a Bioactive Ceramic Spacer and the Change in Load-Sharing of Spinal Instrumentation

Ceramic anterior lumbar interbody arthrodesis was performed using an in vivo sheep model. Observations of fusion status and the load-sharing of spinal instrumentation were studied at sequential intervals for 1 year after surgery. To elucidate the healing process of spinal arthrodesis performed with a bioactive ceramic spacer and the change in load-sharing of anterior spinal instrumentation. With the improved development of spinal instrumentation, anterior spinal arthrodesis has become a standard spinal reconstruction technique; however, the mechanistic basis underlying the healing process is not well documented. Moreover, it remains unclear how load-distribution through the fusion mass and spinal instrumentation change throughout the healing process. Using 24 sheep, a two-level anterior lumbar interbody fusion (L2-L3, L4-L5) was performed using a smooth surface and a porous surface-modified bioactive ceramic, with each segment instrumented using a one-rod anterior spinal instrumentation system. Four animals each were killed at 2, 4, 8, 12, 24, and 52 weeks after surgery. Postmortem analysis included quantification of anterior rod strain under multidirectional flexibility testing and radiographic and histologic analyses of the arthrodesed segments. From 0 to 8 weeks after surgery, the bending strain of the rod gradually decreased despite no obvious bone formation. From 8 to 24 weeks after surgery, the rod strain markedly decreased with the development of bridging trabeculated bone formation between vertebral bodies. After 24 weeks after surgery, minimal changes were observed in rod strain; however, the fusion mass volumetrically increased with corresponding facet joint atrophy. The porous surface-modification of ceramic did not influence the histologic healing process, despite the improvement of interface osseous union rate. In anterior spinal arthrodesis, spinal instrumentation is mainly exposed to bending stress, with decreased load-sharing with corresponding development of the spinal fusion. Continuous bone remodeling of the anterior fusion mass results in concurrent decreases in spinal instrumentation and posterior spinal element load-transmission. The principal healing mechanism of ceramic anterior interbody spinal fusion is not an osseous union between the ceramic and vertebral body, but bridging bone formation around the ceramic, which directly connects the vertebral bodies above and below the disc.

Posterior instrumentation using compressive laminar hooks and anterior interbody arthrodesis for the treatment of tuberculosis of the lower lumbar spine.

A retrospective review with clinical and radiologic assessment was conducted. To demonstrate the feasibility of posterior short segment augmentation with lamina hook and anterior lumbar interbody arthrodesis in tuberculosis of the lumbar spine by evaluating clinical results, fusion status, and sagittal angle. There are few articles in the literature describing circumferential treatment of lumbar tuberculosis. We have had significant experience with a uniform operative technique for the treatment of this relatively rare condition and report our results with a minimum 2-year follow-up. Twenty-three patients with tuberculosis of the lower lumbar spine underwent posterior instrumentation with laminar hooks and anterior interbody arthrodesis by a single surgeon. The clinical outcomes were evaluated with preoperative and postoperative questionnaires, and the radiographs were independently analyzed with respect to fusion status and sagittal angle. RESULTS.: The mean follow-up period was 28.7 months (range, 24-39 months). The average preoperative, immediate postoperative, and final follow-up sagittal angles were 2.7 degrees, -14.1 degrees, and -11.5 degrees, respectively. There was a mean reduction of 16.7 degrees (range, 9 degrees-23 degrees) after surgery. Two patients had a correction loss more than 5 degrees during the follow-up period. Bony fusion was obtained in all patients. There was no recurrence of the disease. CONCLUSION.: This technique appears to be effective in stabilizing the vertebrae, restoring lordosis, achieving a solid fusion, and improving clinical outcome without sacrificing additional motion segments.

Laparoscopic Anterior Spinal Arthrodesis with rhBMP-2 in a Titanium Interbody Threaded Cage

Anterior lumbar interbody arthrodesis is commonly performed for conditions involving infection, deformity, and instability. The purpose of this investigation was to determine the effective dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute inside a titanium threaded interbody fusion cage using a nonhuman primate model of laparoscopic anterior lumbar interbody arthrodesis. Eight adult rhesus monkeys underwent laparoscopic exposure of the lumbosacral spine followed by insertion of a hollow titanium threaded cylindrical cage (Sofamor-Danek, Memphis, TN, U.S.A.). Before insertion, the chamber of the cage was filled with a collagen sponge delivery vehicle soaked with either 0 mg/ml (sham, buffer only), 0.75 mg/ml (low dose), or 1.5 mg/ml (high dose) of rhBMP-2 (Genetics Institute, Cambridge, MA, U.S.A.). Fusions were evaluated in a blinded fashion with plain radiographs and computed tomography (CT) scans 12 and 24 weeks after surgery, and by manual palpation and histology after euthanasia 24 weeks after surgery. All five monkeys treated with a cage filled with rhBMP-2 obtained a solid fusion as assessed by manual palpation. The two monkeys that received no growth factor did not achieve solid fusions. Plain radiographs were of limited value, with fusions best assessed on sagittally reconstructed CT scans. Scans from the two animals treated without growth factor showed ingrowth of bone only into the outer edges of the cage, but not through the center. Scans from the rhBMP-2-treated animals demonstrated arthrodesis with continuous bone growth through the cage. Histologic analysis demonstrated normal mature trabecular bone surrounding and growing through the cages, which correlated with the CT scan findings. We conclude that rhBMP-2 delivered in a threaded titanium interbody cage can serve as a bone graft substitute in a nonhuman primate model. Sagittal reconstructed CT may be a better method to assess for fusion with this device.

Video-assisted lateral intertransverse process arthrodesis. Validation of a new minimally invasive lumbar spinal fusion technique in the rabbit and nonhuman primate (rhesus) models.

Cadaveric anatomic and in vivo survival animal studies were performed to develop a new arthrodesis technique for the lumbar spine. To examine the feasibility, efficacy, and safety of a minimally invasive lumbar intertransverse process arthrodesis technique using an osteoinductive growth factor (rhBMP-2) delivered in a collagen sponge carrier. The technique was first developed using a rabbit model and modified for the nonhuman primate (rhesus monkey), a larger animal with the most similar bone biology to humans. The morbidity of conventional posterolateral lumbar intertransverse process arthrodesis includes graft donor site morbidity; paraspinal muscle devascularization, denervation, and scarring and nonunion in up to 36% of patients. Minimally invasive anterior lumbar interbody arthrodesis techniques have been developed, but these often require a metal implant and carry risks to major vessels and development of retrograde ejaculation. A minimally invasive technique for posterolateral intertransverse process arthrodesis has not been described previously. In Part 1, we examined seven New Zealand white rabbits and five rhesus monkeys at necropsy and during nonsurvival surgeries to determine the best access routes and to develop special instruments for video-assisted lateral intertransverse process arthrodesis. In Part 2, 38 New Zealand white rabbits underwent L4-L5 intertransverse process arthrodesis: the "OPEN" group (n = 16) underwent a standard open muscle-splitting approach using rhBMP-2 (bone morphogenetic protein) and collagen as a bone graft substitute; the "video-assisted control" group (n = 6) underwent video-assisted lateral intertransverse process arthrodesis with the collagen implant only (no growth factor); and the "video-assisted-BMP" group (n = 16) underwent video-assisted lateral intertransverse process arthrodesis with rhBMP-2 and collagen as the graft material. In Part 3, rhesus monkeys (n = 4) underwent video-assisted lateral intertransverse process arthrodesis using rhBMP-2 and collagen after laminectomy of L4-L5. In Part 1, we identified expedient, minimally invasive routes to the intertransverse process interval appropriate for each species: an intermuscular approach for the rabbit and a lateral, extramuscular approach for the rhesus monkey. In Part 2, all rabbits in the OPEN and video-assisted-BMP groups achieved solid intertransverse process lumbar fusions when assessed at 10 weeks. There were no neurologic impairments nor any difference between the two groups in the frequency of postoperative infection or other complications. None of the animals in the video-assisted control group showed evidence of fusion. In Part 3, exposure, decortication and grafting with rh-BMP-2 and collagen was accomplished successfully in all four monkeys through the video-assisted minimally invasive approach without complications. Video-assisted lateral intertransverse process arthrodesis is a feasible, effective, and safe method of lumbar spinal fusion in the rabbit and rhesus monkey. Use of this arthrodesis procedure will minimize the morbidity of paraspinal muscle denervation and devascularization seen with open intertransverse process fusion techniques, and the use of an osteoinductive growth factor will eliminate the problem of graft donor site morbidity and possibly increase the chances for successful fusion.

Transfacet Screws with Lumbar Interbody Reconstruction

In a biomechanical study using nine cadaveric lumbar motion segments, we evaluated the effect that the insertion of transfacet screws had on stiffness, after the implantation of a threaded spine cage to simulate anterior lumbar interbody arthrodesis. Each motion segment was tested according to a biomechanical loading sequence, which consisted of compression, flexion, extension, right lateral bending, and left lateral bending. This was applied to each motion segment four times as follows: (a) the intact intervertebral joint; (b) after the insertion of an interbody threaded spine cage; (c) after the additional insertion of transfacet screws; and (d) after the removal of the transfacet screws (with the cage still inserted). At each step in the loading sequence, a load-deformation curve was obtained, and from this curve a stiffness value was calculated. The most important finding was the increase in stiffness of the motion segment, particularly in extension, after the insertion of the transfacet screws. This finding suggests that transfacet screws may be useful for stabilizing segments reconstructed with bone graft or cages.

Laparoscopic discectomy with anterior lumbar interbody fusion. A preliminary review.

Patients presenting with L5-S1 anterior column disease with or without herniation into the spinal canal but without stenosis underwent magnetic resonance imaging screening before surgery to determine surgical suitability for laparoscopic anterior lumbar interbody fusion relative to the aortic bifurcation and approach to the disc space. To analyze and evaluate the laparoscopic approach, technique, and benefit of anterior lumbar discectomy and interbody fusion by distraction and compression-loading of autograft only as compared with cage-spacer-enhanced autograft fusion. Advancement in minimally invasive spine surgery techniques has provided options with less morbidity for posterior lumbar procedures. General surgical advancements in laparoscopy and advantages of traditional anterior lumbar interbody fusion, including restoration of disc height and exposure for safe nerve decompression, provided a basis for an integrated procedure that would address anterior column abnormality with low surgical morbidity. Five patients underwent technically successful laparoscopic anterior lumbar interbody fusion with approach to the disc space by an experienced laparoscopic general surgeon. A sixth patient in the study group was unable to undergo laparoscopic fusion because of an iliac vein tear during the surgical approach. After the approach, a spine surgeon followed with complete manual discectomy and interbody autogenous fusion laparoscopically. Two to three Cloward-type dowels were obtained by separate incision from the anterior iliac crest. All patients by 6-month follow-up examination were clinically fused with no motion on flexion-extension radiographs. One patient had slight anterior retropulsion of one dowel without the necessity of reoperation. Laparoscopic L5-S1 anterior lumbar interbody arthrodesis may represent a viable option for patients with abnormality, including anterior column and degenerative disc disease.