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A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion
The Spine Journal 6 (2006) 405–412
A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion Scott H. Kitchel, MD* Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA Received 25 April 2005; accepted 30 September 2005
Abstract
BACKGROUND CONTEXT: Multiple bone graft substitutes for spinal fusion have been studied with varying results. PURPOSE: The purpose of this study was to assess the effectiveness of a mineralized collagen matrix combined with bone marrow, versus autologous bone, in the same patients undergoing a posterior lumbar interbody fusion and an instrumented posterolateral lumbar fusion. STUDY DESIGN/SETTING: A prospective, comparative study. PATIENT SAMPLE: Patients indicated for one-level posterior lumbar interbody fusion and instrumented posterolateral lumbar fusion, serving as self-controls. OUTCOME MEASURES: Thin-cut computed tomographic scans with sagittal reconstruction and plain radiographs, including lateral flexion/extension views were performed and assessed at 12 and 24 months after surgery. Oswestry Disability Index and Visual Analog Scale questionnaires were completed by all patients preoperatively and at 12 and 24 months after surgery. METHODS: After informed consent and failure of nonoperative treatment, 25 consecutive patients requiring one-level instrumented posterolateral fusion combined with posterior interbody fusion were enrolled in the study. Mineralized collagen bone graft substitute combined with bone marrow aspirate was used on one side of the posterolateral fusion, with iliac crest autograft on the contralateral side. RESULTS: A fusion rate of 84% (21/25) was achieved for the autologous bone grafts and 80% (20/25) for the bone graft substitute. The interbody fusion rate was 92% (23/25). Mean Oswestry Disability Index (ODI) scores decreased 57.2% at 12 months and 55.6% at 24 months, compared with baseline. CONCLUSIONS: Mineralized collagen bone graft substitute exhibited similar radiographic results compared with autograft in this model. Further trials incorporating bilateral fusion, as well as posterolateral fusion alone without interbody fusion are warranted to confirm the results of this study. Ó 2006 Elsevier Inc. All rights reserved.
Keywords:
Lumbar spine; Posterior fusion; Bone graft substitute
Introduction Autologous bone harvested from the iliac crest is the gold standard in grafting materials for lumbar spinal fusion. FDA device/drug status: approved for this indication (Healos Bone Graft Substitute). The author is a consultant to DePuy Spine, Inc., Raynham, MA, and received grant research support for this study from DePuy Spine, Inc. * Corresponding author. Orthopedic Spine Associates, 1426 Oak Street, Eugene, OR 97401. Tel.: (541) 686-8353; fax: (541) 343-9387. E-mail address: [email protected] (S.H. Kitchel) 1529-9430/06/$ – see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.spinee.2005.09.013
However, significant rates of postoperative donor site pain and morbidity have been reported in the literature, with some reported rates as high as 30% [1–7]. In addition, many patients underreport the incidence and intensity of postoperative donor site pain to their surgeons [1], suggesting donor site pain may be higher than conventional wisdom suggests. Local autologous bone available after a posterior decompression is an alternative to iliac crest graft. Yet local autologous bone graft is often infiltrated with soft-tissue material [8,9]. This source of bone graft is not available for anterior fusion procedures.
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The primary alternative to autologous bone is allograft, but allograft by itself is widely recognized as an ineffective material as a posterior onlay graft except in cases of instrumented fusion for pediatric deformity [10–16]. Though successful for fusion in some applications, the slight risk of disease transmission from allograft remains, and incorporation and fusion rates in smokers tend to be lower when compared with nonsmokers [17–19]. Bone morphogenetic protein has been approved for use as a bone graft substitute in a cage for anterior lumbar interbody fusion, but bone morphogenetic protein has only been approved for posterior lumbar use as part of a Humanitarian Device Exemption [20]. The ideal bone graft substitute for spinal fusion would have the following characteristics: osteoconductivity; osteoinductivity or osteogenicity; easily formed to custom shapes and sizes; resorbable; easily transported (does not require refrigeration); nonimmunogenic; and provides equivalent rates of fusion when compared with iliac crest bone graft [21]. A commercially available Type I bovine collagen fibrous matrix (DePuy Spine, Raynham, MA) is uniformly coated with hydroxyapatite through a patented mineralization process. The final product is approximately 30% hydroxyapatite by weight and completely radiolucent on plain radiographs. It has an interconnected pore size of 4–200 microns, similar to human cancellous bone. The collagen fibers combined with the pore size provide an osteoconductive matrix for new bone growth (Fig. 1). The hydroxyapatite coating provides protein binding capability
similar to the composition of immature human bone. In addition to it being osteoconductive and resorbable, this mineralized collagen meets all of the criteria for an ideal bone graft replacement with the exception that is had no inherent osteoinductive or osteogenic properties. Therefore, in order to realize its full potential as a bone graft replacement, it should be combined with an osteogenic component. The osteogenicity of bone marrow was first identified by Burwell in 1964 [22]. Burwell demonstrated that the two main sources of new bone formed from ectopically implanted iliac crest bone graft (ICBG) included osteoblasts from the surfaces of grafted bone, and bone marrow cells. The importance of a support matrix for bone marrow cells was further explored by Nade in the 1970s [23–26]. Nade’s studies in a rat model led to the conclusion that osteogenesis required an osteoconductive environment with optimal spatial and chemical configurations for attachment of osteogenic cells. Other bone [27] and synthetic matrices [28– 31] designed to mimic the configuration of bone have been shown to support bone formation when seeded with bone marrow cells. Tay et al. [32] described mineralized collagen (MC) combined with bone marrow aspirate (BMA) in a rabbit posterolateral fusion model with a fusion rate 100% (10/ 10) 8 weeks after surgery. The fusion rate with mineralized collagen alone in this model was 18% (2/11) highlighting the important role that bone marrow plays as a source of osteogenic progenitor cells. In a rabbit long bone critical defect model with MC/BMA, Spiro et al. [33] reported a fusion rate of 100% (20/20) at 24 weeks. In a baboon anterior interbody fusion model with MC/BMA, Griffith et al. [34] reported identical biomechanics, amount of trabecular bone, and fusion rates at both 3 and 6 months when compared with autologous bone. In humans, Grosse et al. [35] reported a randomized study of MC/BMA versus autograft for instrumented posterolateral lumbar fusion. At 12 months the fusion rate was 76.9% (10/13) in the MC/BMA group and 81.3% (13/16) in the autograft group. There was no statistical difference between the groups with respect to fusion rate (p51.00), and no complications in either group. With the experience in animals and humans as background, a prospective pilot study of 25 patients was designed to ascertain the efficacy of MC/BMA as a bone graft substitute in a onelevel, self-controlled, instrumented posterolateral lumbar fusion model.
Materials and methods
Fig. 1. The collagen fibrous matrix is uniformly coated with hydroxyapatite through a patented mineralization process. The final product is approximately 30% hydroxyapatite by weight and completely radiolucent on plain radiographs. It has an interconnected pore size of 4–200 microns, similar to human cancellous bone.
After local institutional review board approval and informed consent, 25 consecutive patients indicated for one-level instrumented posterolateral fusion combined with interbody fusion were enrolled in the study. Primary diagnoses included: degenerative disc disease, isthmic-lytic spondylolisthesis, degenerative spondylolisthesis, and
S.H. Kitchel / The Spine Journal 6 (2006) 405–412
spinal stenosis. There were 14 females and 11 males, with a mean age of 58 years (range536–72). Smokers were excluded from the study. Three patients were under worker’s compensation or litigation, and 15 patients were fully employed at the time of surgery. There were 16 fusion procedures at L4–L5 and 9 at L5–S1. The same surgical approach was used in all patients. Patients were placed in the supine position and appropriately draped and prepared. A midline incision was made and a decompression was performed in standard fashion dependent upon the pathology. Patients in this series had concomitant gross discectomy and posterior lumbar interbody fusion with one obliquely placed threaded cylindrical cage filled with iliac crest bone graft. After bilateral placement of the transpedicular fixation, the MC/BMA graft was prepared by aspirating 10 cc of BMA, in 2-cc increments, from the posterior iliac crest with a syringe attached to an aspiration needle (Fig. 2). Two 5-cc strips of MC were soaked with the BMA in a plastic surgical dish (Fig. 3). From the contralateral side of the iliac crest where the BMA was harvested, 15 cc of corticocancellous bone was harvested. The placement of the MC/BMA graft was randomized to either the left or right side. ICBG was placed on the contralateral side using the standard technique for posterolateral fusion. The same technique for placement of MC/BMA graft was used in all patients. The technique involved rolling one 5-cc strip longitudinally and placing it against the lateral edge of the facet joint. The second 5-cc strip was then placed laterally from transverse process to transverse process. A total of 10 cc of MC/BMA graft was placed (Fig. 4). The wound was closed in layers. Patients were followed on a normal follow-up schedule as with non-study patients, and advanced with activities as tolerated.
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Thin-cut computed tomographic (CT) scans with sagittal reconstruction, and lateral flexion and extension radiographs were obtained at 12 and 24 months after surgery. Radiographic evaluation was performed by an independent radiologist, blinded to the graft assignments. Strict criteria for posterolateral fusion included no motion on flexion/ extension plain radiographs, no loss of internal fixation, with a Grade of ‘‘A’’ on the Lenke scale [36], applied unilaterallydsolid trabecular bridging bone between the transverse processes on CT scan. The interbody fusion was assessed separately using plain radiographs, CT scan, lack of motion on flexion/extension, and lack of radiographic halo. Clinical outcomes were measured with the Oswestry Disability Index based on 100 (ODI) and two 0–10 Visual Analog Scale (VAS) questionnaires (one for back pain, and one for leg pain). Questionnaires were administered preoperatively and at 12 and 24 months postoperatively.
Results The fusion status in all patients was the same with respect to the 12- and 24-month evaluations. A fusion rate of 84% (21/25) was achieved for the autologous bone grafts and 80% (20/25) for the bone graft substitute (Figs. 5 and 6). In a separate assessment using only the plain radiographs, the fusion rates for each group remained unchanged. The interbody fusion rate was 92% (23/25), with the two patients not exhibiting either an interbody fusion or a posterolateral fusion. There was no difference in clinical outcomes between the 21 patients exhibiting at least a unilateral posterior fusion and the 4 patients with
Fig. 2. Aspiration of bone marrow was performed in 2-cc increments to a volume of 10-cc. It is imperative not to draw more than 2-cc of marrow from an aspiration site. Otherwise the osteoprogenitor cells will become diluted in whole blood.
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Fig. 3. Strips of mineralized collagen matrix are soaked in bone marrow aspirate before use as a bone graft substitute.
a nonunion. Of the 15 patients fully employed before surgery, 14 (93.3%) returned to work. Aside from the four nonunions, there were no perioperative or postoperative complications, and no complaints of bone marrow
aspiration site pain. A total of 28% (7/25) of patients complained of donor graft site pain at 24 months. Clinically, mean ODI scores decreased from 42.8 preoperatively, to 18.3 at 12 months and 19.0 at 24 months after
Fig. 4. Placement of the mineralized collagen/bone marrow aspirate graft was performed using the same technique in all patients. (A) One 5-cc strip was rolled longitudinally and placed against the lateral edge of the facet joint. The second 5-cc strip was then placed laterally from transverse process to transverse process. Autograft was used on the contralateral side. (B) A perioperative photograph after placement of two 5-cc strips of mineralized collagen/bone marrow aspirate graft.
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Fig. 5. Sagittal computed tomographic scan at 2 years of a 58-year-old female patient who had a lumbar fusion at L4–L5 with autograft on the left side and mineralized collagen/bone marrow aspirate (MC/BMA) on the right side. There is a clear cleft in the autograft indicating a nonunion on the left side. The MC/BMA on the right shows solid trabecular bridging of bone from transverse process to transverse process. The patient had a 52% reduction in Oswestry Disability Index score at 2 years compared with baseline, and a reduction in back and leg Visual Analog Scale scores of 32% and 70%, respectively. The patient did not work preoperatively.
surgery. This represents a 57.2% mean improvement at 12 months and 55.6% mean improvement at 24 months. With respect to the VAS scores, mean leg pain was 8.9 preoperatively and improved to 2.3 ( 74.2%) and 2.0 ( 77.5%), at 12 and 24 months, respectively. Mean back pain was 7.3 preoperatively with means of 4.3 ( 41.1%) and 4.8 ( 34.2%) at 12 and 24 months, respectively.
Discussion This study described a consecutive series of 25 patients with MC/BMA on one side of a posterolateral instrumented fusion, and iliac crest bone graft on the contralateral side, in the presence of an interbody fusion. The rate of fusion was similar between the MC/BMA fusion sites and the iliac crest fusion sites using reconstructed sagittal CT scans and lateral flexion/extension radiographs at 12 and 24 months after surgery. None of the grafted sites with a nonunion at 12 months went on to fuse at 24 months. Clinical results were comparable to results reported in the literature for instrumented posterolateral lumbar fusion [37–45]. Because ICBG was used in this study, the elimination of donor site pain and morbidity was not a goal of the study design nor an achieved outcome. The study design has a number of limitations. Smokers were excluded from enrollment in the study. Due to the
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Fig. 6. Sagittal computed tomographic scan at 2 years of a 32-year-old male patient who had a lumbar fusion at L4–L5 with autograft on the left side and mineralized collagen/bone marrow aspirate (MC/BMA) on the right side. There is solid trabecular bridging of bone from transverse process to transverse process bilaterally. The patient had a 64% reduction in Oswestry Disability Index score at 2 years compared with baseline, and a reduction in back and leg Visual Analog Scale scores of 40% and 60%, respectively. The patient returned to work at 6 months postoperatively.
small sample size, it was necessary to eliminate variables which could affect the overall results. Patients requiring multilevel fusion were excluded, again to ensure a homogeneous study population. The mean age of the patients in this study was 58 years. This is rather high for a lumbar fusion series. It is possible the increased age affected the fusion rate. However, because the fusion rate for the MC/BMA graft and the ICBG were nearly identical, the increased age of these patients can be factored out of the analysis. Finally, combined posterolateral and interbody fusion is not the ideal model for studying posterolateral lumbar fusion, because of problems with posterior graft resorption as described by Gill and O’Brien [46]. However, in the author’s practice, posterior-only fusions are a rare surgical treatment, and limiting enrollment to this group would have excessively extended the completion time for the study. Motion in the interdiscal space should not be expected in the presence of pedicle screws even in cases of a nonunion [47], and the use of plain radiographs to evaluate lumbar fusion may not be reliable [48–51]. Therefore, the study design included a strict criteria for fusion using thin-cut CT scans with sagittal reconstruction in tandem with plain radiographs. The presence of trabecular bridging bone from transverse process to transverse process was necessary for a graft site to be graded as ‘‘fused’’. Because of the difficulties in obtaining insurance authorization for postoperative CT scans in patients with a good clinical outcome, it may not be possible for surgeons to evaluate fusion using this method in their practices. However, there is evidence that CT evaluation of fusion is more sensitive than plain radiographs [50,52–56].
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One technical note of importance is the bone marrow aspiration procedure. In 1997, Muschler et al. [57] reported that the concentration of nucleated cells in a given volume of bone marrow decreases dramatically at volumes greater than 2 cc. Therefore, it is imperative that aspiration volumes be limited to approximately 2 cc to avoid dilution of the aspirate with whole blood. If this critical step is ignored, the number of osteoprogenitor cells populating the MC graft will be significantly reduced and bony ingrowth may be hindered. There were no complications related to the MC/BMA graft, and this study shows that the potential use of bilateral application of MC/BMA for instrumented posterolateral lumbar fusion may decrease operative time and pain or morbidity associated with harvesting the iliac crest. Further study is necessary using MC/BMA bilaterally in this model, at multiple levels, in smokers, and in patients indicated for different lumbar fusion procedures and patient indications.
References [1] Heary RF, Schlenk RP, Sacchieri TA, et al. Persistent iliac crest donor site pain: independent outcome assessment. Neurosurgery 2002;50: 510–6; discussion 6–7. [2] Fernyhough JC, Schimandle JJ, Weigel MC, et al. Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine 1992;17:1474–80. [3] Hu RW, Bohlman HH. Fracture at the iliac bone graft harvest site after fusion of the spine. Clin Orthop 1994;309:208–13. [4] Keller EE, Triplett WW. Iliac bone grafting: review of 160 consecutive cases. J Oral Maxillofac Surg 1987;45:11–4. [5] Laurie SW, Kaban LB, Mulliken JB, et al. Donor-site morbidity after harvesting rib and iliac bone. Plast Reconstr Surg 1984;73:933–8. [6] Summers BN, Eisenstein SM. Donor site pain from the ilium: a complication of lumbar spine fusion. J Bone Joint Surg Br 1989;71: 677–80. [7] Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma 1989;3:192–5. [8] Togawa D, Bauer TW, Brantigan JW, et al. Bone graft incorporation in radiographically successful human intervertebral body fusion cages. Spine 2001;26:2744–50. [9] Togawa D, Bauer TW, Lieberman IH, et al. Lumbar intervertebral body fusion cages: histological evaluation of clinically failed cages retrieved from humans. J Bone Joint Surg Am 2004;86-A:70–9. [10] Bridwell KH, O’Brien MF, Lenke LG, et al. Posterior spinal fusion supplemented with only allograft bone in paralytic scoliosis. Does it work? Spine 1994;19:2658–66. [11] Grogan DP, Kalen V, Ross TI, et al. Use of allograft bone for posterior spinal fusion in idiopathic scoliosis. Clin Orthop 1999;369: 273–8. [12] Jones KC, Andrish J, Kuivila T, et al. Radiographic outcomes using freeze-dried cancellous allograft bone for posterior spinal fusion in pediatric idiopathic scoliosis. J Pediatr Orthop 2002;22:285–9. [13] Yazici M, Asher MA. Freeze-dried allograft for posterior spinal fusion in patients with neuromuscular spinal deformities. Spine 1997; 22:1467–71. [14] Montgomery DM, Aronson DD, Lee CL, et al. Posterior spinal fusion: allograft versus autograft bone. J Spinal Disord 1990;3:370–5. [15] An HS, Lynch K, Toth J. Prospective comparison of autograft vs. allograft for adult posterolateral lumbar spine fusion: differences among freeze-dried, frozen, and mixed grafts. J Spinal Disord 1995; 8:131–5.
[16] Jorgenson SS, Lowe TG, France J, et al. A prospective analysis of autograft versus allograft in posterolateral lumbar fusion in the same patient: a minimum of 1-year follow-up in 144 patients. Spine 1994;19: 2048–53. [17] Andersen T, Christensen FB, Laursen M, et al. Smoking as a predictor of negative outcome in lumbar spinal fusion. Spine 2001;26:2623–8. [18] Hadley MN, Reddy SV. Smoking and the human vertebral column: a review of the impact of cigarette use on vertebral bone metabolism and spinal fusion. Neurosurgery 1997;41:116–24. [19] Mooney V, McDermott KL, Song J. Effects of smoking and maturation on long-term maintenance of lumbar spinal fusion success. J Spinal Disord 1999;12:380–5. [20] Federal Register: New Humanitarian Device Approval; OP-1 Putty H020008. April 7, 2004. Accessed August 17, 2005. [21] Thalgott JS, Giuffre JM, Klezl Z, et al. Anterior lumbar interbody fusion with titanium mesh cages, coralline hydroxyapatite, and demineralized bone matrix as part of a circumferential fusion. Spine J 2002;2:63–9. [22] Burwell RG. Studies in the transplantation of bone. VII. The fresh composite homograft-autograft of cancellous bone; an analysis of factors leading to osteogenesis in marrow transplants and in marrow-containing bone grafts. J Bone Joint Surg Br 1964;46:110–40. [23] Nade S. Clinical implications of cell function in osteogenesis. A reappraisal of bone-graft surgery. Ann R Coll Surg Engl 1979;61: 189–94. [24] Nade S. Bone-graft surgery reappraised: the contribution of the cell to ultimate success. Br J Surg 1970;57:752–6. [25] Nade S, Burwell RG. Decalcified bone as a substrate for osteogenesis: an appraisal of the interrelation of bone and marrow in combined grafts. J Bone Joint Surg Br 1977;59:189–96. [26] Nade S. Osteogenesis after bone and bone marrow transplantation. II. The initial cellular events following transplantation of decalcified allografts of cancellous bone. Acta Orthop Scand 1977;48:572–9. [27] Salama R, Burwell RD, Dickson IR. Recombined grafts of bone and marrow: the beneficial effect upon osteogenesis of impregnating xenograft (heterograft) bone with autologous red marrow. J Bone Joint Surg Br 1973;55:402–17. [28] Okumura M, Ohgushi H, Tamai S. Bonding osteogenesis in coralline hydroxyapatite combined with bone marrow cells. Biomaterials 1991;12:411–6. [29] Ohgushi H, Okumura M, Tamai S, et al. Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparative histomorphometric study of ectopic bone formation. J Biomed Mater Res 1990;24:1563–70. [30] Nade S, Armstrong L, McCartney E, et al. Osteogenesis after bone and bone marrow transplantation. The ability of ceramic materials to sustain osteogenesis from transplanted bone marrow cells: preliminary studies. Clin Orthop 1983;181:255–63. [31] Ohgushi H, Goldberg VM, Caplan AI. Repair of bone defects with marrow cells and porous ceramic: experiments in rats. Acta Orthop Scand 1989;60:334–9. [32] Tay BK, Le AX, Heilman M, et al. Use of a collagen–hydroxyapatite matrix in spinal fusion: a rabbit model. Spine 1998;23:2276–81. [33] Spiro R, Pacetti S, Thompson A, et al. Evaluation of a new mineralized collagen bone grafting matrix in a long bone critical defect model. Paper presented at: 43rd Meeting of the Orthopaedic Research Society; February 9–11, 1997; San Francisco, CA. [34] Griffith S, Criscitello A, Cunningham B, et al. Non-human primate evaluation of an osteoconductive bone substitute in an interbody fusion cage. Paper presented at: EuroSpine; September 7–11, 1999; Munich, Germany. [35] Grosse S, Argenson C, Tavna A, et al. Mineralized collagen as a replacement for autogenous bone in posterolateral lumbar spinal fusion. Paper presented at: EuroSpine; September 7–11, 1999; Munich, Germany. [36] Lenke LG, Bridwell KH, Bullis D, et al. Results of in situ fusion for isthmic spondylolisthesis. J Spinal Disord 1992;5:433–42.
S.H. Kitchel / The Spine Journal 6 (2006) 405–412 [37] Resnick DK, Choudhri TF, Dailey AT, et al. Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 12: pedicle screw fixation as an adjunct to posterolateral fusion for low-back pain. J Neurosurg Spine 2005;2:700–6. [38] Kho VK, Chen WC. The results of posterolateral lumbar fusion with bone chips from laminectomy in patients with lumbar spondylolisthesis. J Chin Med Assoc 2004;67:575–8. [39] Ekman P, Moller H, Hedlund R. The long-term effect of posterolateral fusion in adult isthmic spondylolisthesis: a randomized controlled study. Spine J 2005;5:36–44. [40] Cammisa FP Jr, Lowery G, Garfin SR, et al. Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine fusion: a prospective controlled trial employing a sideby-side comparison in the same patient. Spine 2004;29:660–6. [41] Thalgott JS, Giuffre JM, Fritts K, et al. Instrumented posterolateral lumbar fusion using coralline hydroxyapatite with or without demineralized bone matrix, as an adjunct to autologous bone. Spine J 2001;1:131–7. [42] Madan SS, Harley JM, Boeree NR. Circumferential and posterolateral fusion for lumbar disc disease. Clin Orthop Relat Res 2003;409: 114–23. [43] Gehrchen PM, Dahl B, Katonis P, et al. No difference in clinical outcome after posterolateral lumbar fusion between patients with isthmic spondylolisthesis and those with degenerative disc disease using pedicle screw instrumentation: a comparative study of 112 patients with 4 years of follow-up. Eur Spine J 2002;11:423–7. [44] Kimura I, Shingu H, Murata M, et al. Lumbar posterolateral fusion alone or with transpedicular instrumentation in L4–L5 degenerative spondylolisthesis. J Spinal Disord 2001;14:301–10. [45] Hadley MN. Posterolateral fusion of the lumbar spine: rationale, indications, techniques, and results. Clin Neurosurg 2000;47: 483–94. [46] Gill K, O’Brien JP. Observations of resorption of the posterior lateral bone graft in combined anterior and posterior lumbar fusion. Spine 1993;18:1885–9.
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[47] Larsen JM, Rimoldi RL, Capen DA, et al. Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings. J Spinal Disord 1996;9:117–20. [48] Chafetz N, Cann CE, Morris JM, et al. Pseudarthrosis following lumbar fusion: detection by direct coronal CT scanning. Radiology 1987; 162:803–5. [49] Miyata S, Kambara K. [Bone union after lumbar postero-lateral fusion: comparative evaluation by x-ray and CT]. Nippon Seikeigeka Gakkai Zasshi 1994;68:1023–32. [50] Siambanes D, Mather S. Comparison of plain radiographs and CT scans in instrumented posterior lumbar interbody fusion. Orthopedics 1998;21:165–7. [51] Knop C, Bastian L, Lange U, et al. [Transpedicular fusion of the thoraco-lumbar junction. Clinical, radiographic and CT results]. Orthopade 1999;28:703–13. [52] Cook SD, Patron LP, Christakis PM, et al. Comparison of methods for determining the presence and extent of anterior lumbar interbody fusion. Spine 2004;29:1118–23. [53] Epstein NE, Silvergleide RS. Documenting fusion following anterior cervical surgery: a comparison of roentgenogram versus two-dimensional computed tomographic findings. J Spinal Disord Tech 2003; 16:243–7. [54] Santos ER, Goss DG, Morcom RK, et al. Radiologic assessment of interbody fusion using carbon fiber cages. Spine 2003;28:997–1001. [55] Shah RR, Mohammed S, Saifuddin A, et al. Comparison of plain radiographs with CT scan to evaluate interbody fusion following the use of titanium interbody cages and transpedicular instrumentation. Eur Spine J 2003;12:378–85. [56] Tullberg T, Brandt B, Rydberg J, et al. Fusion rate after posterior lumbar interbody fusion with carbon fiber implant: 1-year followup of 51 patients. Eur Spine J 1996;5:178–82. [57] Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am 1997;79:1699–709.
COMMENTARY Harvinder S. Sandhu, MD, MBA, New York, NY
The author has successfully described some, but not all, of the shortcomings of his prospective pilot trial evaluating the use of mineralized collagen and bone marrow aspirate (MC/BMA) for posterolateral spinal fusion. The study was designed to compare the use of MC/BMA for unilateral lumbar transverse process fusion with the use of iliac crest bone graft on the contralateral transverse processes in pedicle screw instrumented patients who were also receiving posterior lumbar interbody fusions with cages filled with iliac crest bone graft. Although the author is rightly concerned with his small sample size and the exclusion of subpopulations such as smokers, I am concerned with more fundamental issues such as study design and validity of conclusions. First, the experimental and control treatments are not independent and there is a likely bias toward equivalence. Disregarding the effect of the interbody intervention, one can speculate that the presence of a unilateral transverse process fusion, perhaps due to iliac crest grafting, will affect
the behavior on the opposite side. The effect may include resorption along the lateral portions of the inter-transverse space but also an increased probability of ankylosis along the facet joint. Indeed, the computed tomographic images provided in the article suggest just thatdfusion along the facet and pars rather than a frank bony bridge along the transverse processes. Second, the presence of a 360 intervention essentially delegates the biologically superior interbody space as the primary site for segmental arthrodesis. The immediate probable stress shielding of the posterior column caused by the interbody cage further diminishes the relevance of the biologic activity along the posterolateral gutters. The author’s explanation for confounding his study design with interbody fusion is that the procedure is customary in his practice. In my opinion, the conclusions of this paper would have been strengthened with a better study design. This is essentially a biologic study evaluating an alternative bone graft substitute for posterolateral lumbar fusion.
A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion Scott H. Kitchel, MD* Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA Received 25 April 2005; accepted 30 September 2005
Abstract
BACKGROUND CONTEXT: Multiple bone graft substitutes for spinal fusion have been studied with varying results. PURPOSE: The purpose of this study was to assess the effectiveness of a mineralized collagen matrix combined with bone marrow, versus autologous bone, in the same patients undergoing a posterior lumbar interbody fusion and an instrumented posterolateral lumbar fusion. STUDY DESIGN/SETTING: A prospective, comparative study. PATIENT SAMPLE: Patients indicated for one-level posterior lumbar interbody fusion and instrumented posterolateral lumbar fusion, serving as self-controls. OUTCOME MEASURES: Thin-cut computed tomographic scans with sagittal reconstruction and plain radiographs, including lateral flexion/extension views were performed and assessed at 12 and 24 months after surgery. Oswestry Disability Index and Visual Analog Scale questionnaires were completed by all patients preoperatively and at 12 and 24 months after surgery. METHODS: After informed consent and failure of nonoperative treatment, 25 consecutive patients requiring one-level instrumented posterolateral fusion combined with posterior interbody fusion were enrolled in the study. Mineralized collagen bone graft substitute combined with bone marrow aspirate was used on one side of the posterolateral fusion, with iliac crest autograft on the contralateral side. RESULTS: A fusion rate of 84% (21/25) was achieved for the autologous bone grafts and 80% (20/25) for the bone graft substitute. The interbody fusion rate was 92% (23/25). Mean Oswestry Disability Index (ODI) scores decreased 57.2% at 12 months and 55.6% at 24 months, compared with baseline. CONCLUSIONS: Mineralized collagen bone graft substitute exhibited similar radiographic results compared with autograft in this model. Further trials incorporating bilateral fusion, as well as posterolateral fusion alone without interbody fusion are warranted to confirm the results of this study. Ó 2006 Elsevier Inc. All rights reserved.
Keywords:
Lumbar spine; Posterior fusion; Bone graft substitute
Introduction Autologous bone harvested from the iliac crest is the gold standard in grafting materials for lumbar spinal fusion. FDA device/drug status: approved for this indication (Healos Bone Graft Substitute). The author is a consultant to DePuy Spine, Inc., Raynham, MA, and received grant research support for this study from DePuy Spine, Inc. * Corresponding author. Orthopedic Spine Associates, 1426 Oak Street, Eugene, OR 97401. Tel.: (541) 686-8353; fax: (541) 343-9387. E-mail address: [email protected] (S.H. Kitchel) 1529-9430/06/$ – see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.spinee.2005.09.013
However, significant rates of postoperative donor site pain and morbidity have been reported in the literature, with some reported rates as high as 30% [1–7]. In addition, many patients underreport the incidence and intensity of postoperative donor site pain to their surgeons [1], suggesting donor site pain may be higher than conventional wisdom suggests. Local autologous bone available after a posterior decompression is an alternative to iliac crest graft. Yet local autologous bone graft is often infiltrated with soft-tissue material [8,9]. This source of bone graft is not available for anterior fusion procedures.
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The primary alternative to autologous bone is allograft, but allograft by itself is widely recognized as an ineffective material as a posterior onlay graft except in cases of instrumented fusion for pediatric deformity [10–16]. Though successful for fusion in some applications, the slight risk of disease transmission from allograft remains, and incorporation and fusion rates in smokers tend to be lower when compared with nonsmokers [17–19]. Bone morphogenetic protein has been approved for use as a bone graft substitute in a cage for anterior lumbar interbody fusion, but bone morphogenetic protein has only been approved for posterior lumbar use as part of a Humanitarian Device Exemption [20]. The ideal bone graft substitute for spinal fusion would have the following characteristics: osteoconductivity; osteoinductivity or osteogenicity; easily formed to custom shapes and sizes; resorbable; easily transported (does not require refrigeration); nonimmunogenic; and provides equivalent rates of fusion when compared with iliac crest bone graft [21]. A commercially available Type I bovine collagen fibrous matrix (DePuy Spine, Raynham, MA) is uniformly coated with hydroxyapatite through a patented mineralization process. The final product is approximately 30% hydroxyapatite by weight and completely radiolucent on plain radiographs. It has an interconnected pore size of 4–200 microns, similar to human cancellous bone. The collagen fibers combined with the pore size provide an osteoconductive matrix for new bone growth (Fig. 1). The hydroxyapatite coating provides protein binding capability
similar to the composition of immature human bone. In addition to it being osteoconductive and resorbable, this mineralized collagen meets all of the criteria for an ideal bone graft replacement with the exception that is had no inherent osteoinductive or osteogenic properties. Therefore, in order to realize its full potential as a bone graft replacement, it should be combined with an osteogenic component. The osteogenicity of bone marrow was first identified by Burwell in 1964 [22]. Burwell demonstrated that the two main sources of new bone formed from ectopically implanted iliac crest bone graft (ICBG) included osteoblasts from the surfaces of grafted bone, and bone marrow cells. The importance of a support matrix for bone marrow cells was further explored by Nade in the 1970s [23–26]. Nade’s studies in a rat model led to the conclusion that osteogenesis required an osteoconductive environment with optimal spatial and chemical configurations for attachment of osteogenic cells. Other bone [27] and synthetic matrices [28– 31] designed to mimic the configuration of bone have been shown to support bone formation when seeded with bone marrow cells. Tay et al. [32] described mineralized collagen (MC) combined with bone marrow aspirate (BMA) in a rabbit posterolateral fusion model with a fusion rate 100% (10/ 10) 8 weeks after surgery. The fusion rate with mineralized collagen alone in this model was 18% (2/11) highlighting the important role that bone marrow plays as a source of osteogenic progenitor cells. In a rabbit long bone critical defect model with MC/BMA, Spiro et al. [33] reported a fusion rate of 100% (20/20) at 24 weeks. In a baboon anterior interbody fusion model with MC/BMA, Griffith et al. [34] reported identical biomechanics, amount of trabecular bone, and fusion rates at both 3 and 6 months when compared with autologous bone. In humans, Grosse et al. [35] reported a randomized study of MC/BMA versus autograft for instrumented posterolateral lumbar fusion. At 12 months the fusion rate was 76.9% (10/13) in the MC/BMA group and 81.3% (13/16) in the autograft group. There was no statistical difference between the groups with respect to fusion rate (p51.00), and no complications in either group. With the experience in animals and humans as background, a prospective pilot study of 25 patients was designed to ascertain the efficacy of MC/BMA as a bone graft substitute in a onelevel, self-controlled, instrumented posterolateral lumbar fusion model.
Materials and methods
Fig. 1. The collagen fibrous matrix is uniformly coated with hydroxyapatite through a patented mineralization process. The final product is approximately 30% hydroxyapatite by weight and completely radiolucent on plain radiographs. It has an interconnected pore size of 4–200 microns, similar to human cancellous bone.
After local institutional review board approval and informed consent, 25 consecutive patients indicated for one-level instrumented posterolateral fusion combined with interbody fusion were enrolled in the study. Primary diagnoses included: degenerative disc disease, isthmic-lytic spondylolisthesis, degenerative spondylolisthesis, and
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spinal stenosis. There were 14 females and 11 males, with a mean age of 58 years (range536–72). Smokers were excluded from the study. Three patients were under worker’s compensation or litigation, and 15 patients were fully employed at the time of surgery. There were 16 fusion procedures at L4–L5 and 9 at L5–S1. The same surgical approach was used in all patients. Patients were placed in the supine position and appropriately draped and prepared. A midline incision was made and a decompression was performed in standard fashion dependent upon the pathology. Patients in this series had concomitant gross discectomy and posterior lumbar interbody fusion with one obliquely placed threaded cylindrical cage filled with iliac crest bone graft. After bilateral placement of the transpedicular fixation, the MC/BMA graft was prepared by aspirating 10 cc of BMA, in 2-cc increments, from the posterior iliac crest with a syringe attached to an aspiration needle (Fig. 2). Two 5-cc strips of MC were soaked with the BMA in a plastic surgical dish (Fig. 3). From the contralateral side of the iliac crest where the BMA was harvested, 15 cc of corticocancellous bone was harvested. The placement of the MC/BMA graft was randomized to either the left or right side. ICBG was placed on the contralateral side using the standard technique for posterolateral fusion. The same technique for placement of MC/BMA graft was used in all patients. The technique involved rolling one 5-cc strip longitudinally and placing it against the lateral edge of the facet joint. The second 5-cc strip was then placed laterally from transverse process to transverse process. A total of 10 cc of MC/BMA graft was placed (Fig. 4). The wound was closed in layers. Patients were followed on a normal follow-up schedule as with non-study patients, and advanced with activities as tolerated.
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Thin-cut computed tomographic (CT) scans with sagittal reconstruction, and lateral flexion and extension radiographs were obtained at 12 and 24 months after surgery. Radiographic evaluation was performed by an independent radiologist, blinded to the graft assignments. Strict criteria for posterolateral fusion included no motion on flexion/ extension plain radiographs, no loss of internal fixation, with a Grade of ‘‘A’’ on the Lenke scale [36], applied unilaterallydsolid trabecular bridging bone between the transverse processes on CT scan. The interbody fusion was assessed separately using plain radiographs, CT scan, lack of motion on flexion/extension, and lack of radiographic halo. Clinical outcomes were measured with the Oswestry Disability Index based on 100 (ODI) and two 0–10 Visual Analog Scale (VAS) questionnaires (one for back pain, and one for leg pain). Questionnaires were administered preoperatively and at 12 and 24 months postoperatively.
Results The fusion status in all patients was the same with respect to the 12- and 24-month evaluations. A fusion rate of 84% (21/25) was achieved for the autologous bone grafts and 80% (20/25) for the bone graft substitute (Figs. 5 and 6). In a separate assessment using only the plain radiographs, the fusion rates for each group remained unchanged. The interbody fusion rate was 92% (23/25), with the two patients not exhibiting either an interbody fusion or a posterolateral fusion. There was no difference in clinical outcomes between the 21 patients exhibiting at least a unilateral posterior fusion and the 4 patients with
Fig. 2. Aspiration of bone marrow was performed in 2-cc increments to a volume of 10-cc. It is imperative not to draw more than 2-cc of marrow from an aspiration site. Otherwise the osteoprogenitor cells will become diluted in whole blood.
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Fig. 3. Strips of mineralized collagen matrix are soaked in bone marrow aspirate before use as a bone graft substitute.
a nonunion. Of the 15 patients fully employed before surgery, 14 (93.3%) returned to work. Aside from the four nonunions, there were no perioperative or postoperative complications, and no complaints of bone marrow
aspiration site pain. A total of 28% (7/25) of patients complained of donor graft site pain at 24 months. Clinically, mean ODI scores decreased from 42.8 preoperatively, to 18.3 at 12 months and 19.0 at 24 months after
Fig. 4. Placement of the mineralized collagen/bone marrow aspirate graft was performed using the same technique in all patients. (A) One 5-cc strip was rolled longitudinally and placed against the lateral edge of the facet joint. The second 5-cc strip was then placed laterally from transverse process to transverse process. Autograft was used on the contralateral side. (B) A perioperative photograph after placement of two 5-cc strips of mineralized collagen/bone marrow aspirate graft.
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Fig. 5. Sagittal computed tomographic scan at 2 years of a 58-year-old female patient who had a lumbar fusion at L4–L5 with autograft on the left side and mineralized collagen/bone marrow aspirate (MC/BMA) on the right side. There is a clear cleft in the autograft indicating a nonunion on the left side. The MC/BMA on the right shows solid trabecular bridging of bone from transverse process to transverse process. The patient had a 52% reduction in Oswestry Disability Index score at 2 years compared with baseline, and a reduction in back and leg Visual Analog Scale scores of 32% and 70%, respectively. The patient did not work preoperatively.
surgery. This represents a 57.2% mean improvement at 12 months and 55.6% mean improvement at 24 months. With respect to the VAS scores, mean leg pain was 8.9 preoperatively and improved to 2.3 ( 74.2%) and 2.0 ( 77.5%), at 12 and 24 months, respectively. Mean back pain was 7.3 preoperatively with means of 4.3 ( 41.1%) and 4.8 ( 34.2%) at 12 and 24 months, respectively.
Discussion This study described a consecutive series of 25 patients with MC/BMA on one side of a posterolateral instrumented fusion, and iliac crest bone graft on the contralateral side, in the presence of an interbody fusion. The rate of fusion was similar between the MC/BMA fusion sites and the iliac crest fusion sites using reconstructed sagittal CT scans and lateral flexion/extension radiographs at 12 and 24 months after surgery. None of the grafted sites with a nonunion at 12 months went on to fuse at 24 months. Clinical results were comparable to results reported in the literature for instrumented posterolateral lumbar fusion [37–45]. Because ICBG was used in this study, the elimination of donor site pain and morbidity was not a goal of the study design nor an achieved outcome. The study design has a number of limitations. Smokers were excluded from enrollment in the study. Due to the
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Fig. 6. Sagittal computed tomographic scan at 2 years of a 32-year-old male patient who had a lumbar fusion at L4–L5 with autograft on the left side and mineralized collagen/bone marrow aspirate (MC/BMA) on the right side. There is solid trabecular bridging of bone from transverse process to transverse process bilaterally. The patient had a 64% reduction in Oswestry Disability Index score at 2 years compared with baseline, and a reduction in back and leg Visual Analog Scale scores of 40% and 60%, respectively. The patient returned to work at 6 months postoperatively.
small sample size, it was necessary to eliminate variables which could affect the overall results. Patients requiring multilevel fusion were excluded, again to ensure a homogeneous study population. The mean age of the patients in this study was 58 years. This is rather high for a lumbar fusion series. It is possible the increased age affected the fusion rate. However, because the fusion rate for the MC/BMA graft and the ICBG were nearly identical, the increased age of these patients can be factored out of the analysis. Finally, combined posterolateral and interbody fusion is not the ideal model for studying posterolateral lumbar fusion, because of problems with posterior graft resorption as described by Gill and O’Brien [46]. However, in the author’s practice, posterior-only fusions are a rare surgical treatment, and limiting enrollment to this group would have excessively extended the completion time for the study. Motion in the interdiscal space should not be expected in the presence of pedicle screws even in cases of a nonunion [47], and the use of plain radiographs to evaluate lumbar fusion may not be reliable [48–51]. Therefore, the study design included a strict criteria for fusion using thin-cut CT scans with sagittal reconstruction in tandem with plain radiographs. The presence of trabecular bridging bone from transverse process to transverse process was necessary for a graft site to be graded as ‘‘fused’’. Because of the difficulties in obtaining insurance authorization for postoperative CT scans in patients with a good clinical outcome, it may not be possible for surgeons to evaluate fusion using this method in their practices. However, there is evidence that CT evaluation of fusion is more sensitive than plain radiographs [50,52–56].
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One technical note of importance is the bone marrow aspiration procedure. In 1997, Muschler et al. [57] reported that the concentration of nucleated cells in a given volume of bone marrow decreases dramatically at volumes greater than 2 cc. Therefore, it is imperative that aspiration volumes be limited to approximately 2 cc to avoid dilution of the aspirate with whole blood. If this critical step is ignored, the number of osteoprogenitor cells populating the MC graft will be significantly reduced and bony ingrowth may be hindered. There were no complications related to the MC/BMA graft, and this study shows that the potential use of bilateral application of MC/BMA for instrumented posterolateral lumbar fusion may decrease operative time and pain or morbidity associated with harvesting the iliac crest. Further study is necessary using MC/BMA bilaterally in this model, at multiple levels, in smokers, and in patients indicated for different lumbar fusion procedures and patient indications.
References [1] Heary RF, Schlenk RP, Sacchieri TA, et al. Persistent iliac crest donor site pain: independent outcome assessment. Neurosurgery 2002;50: 510–6; discussion 6–7. [2] Fernyhough JC, Schimandle JJ, Weigel MC, et al. Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine 1992;17:1474–80. [3] Hu RW, Bohlman HH. Fracture at the iliac bone graft harvest site after fusion of the spine. Clin Orthop 1994;309:208–13. [4] Keller EE, Triplett WW. Iliac bone grafting: review of 160 consecutive cases. J Oral Maxillofac Surg 1987;45:11–4. [5] Laurie SW, Kaban LB, Mulliken JB, et al. Donor-site morbidity after harvesting rib and iliac bone. Plast Reconstr Surg 1984;73:933–8. [6] Summers BN, Eisenstein SM. Donor site pain from the ilium: a complication of lumbar spine fusion. J Bone Joint Surg Br 1989;71: 677–80. [7] Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop Trauma 1989;3:192–5. [8] Togawa D, Bauer TW, Brantigan JW, et al. Bone graft incorporation in radiographically successful human intervertebral body fusion cages. Spine 2001;26:2744–50. [9] Togawa D, Bauer TW, Lieberman IH, et al. Lumbar intervertebral body fusion cages: histological evaluation of clinically failed cages retrieved from humans. J Bone Joint Surg Am 2004;86-A:70–9. [10] Bridwell KH, O’Brien MF, Lenke LG, et al. Posterior spinal fusion supplemented with only allograft bone in paralytic scoliosis. Does it work? Spine 1994;19:2658–66. [11] Grogan DP, Kalen V, Ross TI, et al. Use of allograft bone for posterior spinal fusion in idiopathic scoliosis. Clin Orthop 1999;369: 273–8. [12] Jones KC, Andrish J, Kuivila T, et al. Radiographic outcomes using freeze-dried cancellous allograft bone for posterior spinal fusion in pediatric idiopathic scoliosis. J Pediatr Orthop 2002;22:285–9. [13] Yazici M, Asher MA. Freeze-dried allograft for posterior spinal fusion in patients with neuromuscular spinal deformities. Spine 1997; 22:1467–71. [14] Montgomery DM, Aronson DD, Lee CL, et al. Posterior spinal fusion: allograft versus autograft bone. J Spinal Disord 1990;3:370–5. [15] An HS, Lynch K, Toth J. Prospective comparison of autograft vs. allograft for adult posterolateral lumbar spine fusion: differences among freeze-dried, frozen, and mixed grafts. J Spinal Disord 1995; 8:131–5.
[16] Jorgenson SS, Lowe TG, France J, et al. A prospective analysis of autograft versus allograft in posterolateral lumbar fusion in the same patient: a minimum of 1-year follow-up in 144 patients. Spine 1994;19: 2048–53. [17] Andersen T, Christensen FB, Laursen M, et al. Smoking as a predictor of negative outcome in lumbar spinal fusion. Spine 2001;26:2623–8. [18] Hadley MN, Reddy SV. Smoking and the human vertebral column: a review of the impact of cigarette use on vertebral bone metabolism and spinal fusion. Neurosurgery 1997;41:116–24. [19] Mooney V, McDermott KL, Song J. Effects of smoking and maturation on long-term maintenance of lumbar spinal fusion success. J Spinal Disord 1999;12:380–5. [20] Federal Register: New Humanitarian Device Approval; OP-1 Putty H020008. April 7, 2004. Accessed August 17, 2005. [21] Thalgott JS, Giuffre JM, Klezl Z, et al. Anterior lumbar interbody fusion with titanium mesh cages, coralline hydroxyapatite, and demineralized bone matrix as part of a circumferential fusion. Spine J 2002;2:63–9. [22] Burwell RG. Studies in the transplantation of bone. VII. The fresh composite homograft-autograft of cancellous bone; an analysis of factors leading to osteogenesis in marrow transplants and in marrow-containing bone grafts. J Bone Joint Surg Br 1964;46:110–40. [23] Nade S. Clinical implications of cell function in osteogenesis. A reappraisal of bone-graft surgery. Ann R Coll Surg Engl 1979;61: 189–94. [24] Nade S. Bone-graft surgery reappraised: the contribution of the cell to ultimate success. Br J Surg 1970;57:752–6. [25] Nade S, Burwell RG. Decalcified bone as a substrate for osteogenesis: an appraisal of the interrelation of bone and marrow in combined grafts. J Bone Joint Surg Br 1977;59:189–96. [26] Nade S. Osteogenesis after bone and bone marrow transplantation. II. The initial cellular events following transplantation of decalcified allografts of cancellous bone. Acta Orthop Scand 1977;48:572–9. [27] Salama R, Burwell RD, Dickson IR. Recombined grafts of bone and marrow: the beneficial effect upon osteogenesis of impregnating xenograft (heterograft) bone with autologous red marrow. J Bone Joint Surg Br 1973;55:402–17. [28] Okumura M, Ohgushi H, Tamai S. Bonding osteogenesis in coralline hydroxyapatite combined with bone marrow cells. Biomaterials 1991;12:411–6. [29] Ohgushi H, Okumura M, Tamai S, et al. Marrow cell induced osteogenesis in porous hydroxyapatite and tricalcium phosphate: a comparative histomorphometric study of ectopic bone formation. J Biomed Mater Res 1990;24:1563–70. [30] Nade S, Armstrong L, McCartney E, et al. Osteogenesis after bone and bone marrow transplantation. The ability of ceramic materials to sustain osteogenesis from transplanted bone marrow cells: preliminary studies. Clin Orthop 1983;181:255–63. [31] Ohgushi H, Goldberg VM, Caplan AI. Repair of bone defects with marrow cells and porous ceramic: experiments in rats. Acta Orthop Scand 1989;60:334–9. [32] Tay BK, Le AX, Heilman M, et al. Use of a collagen–hydroxyapatite matrix in spinal fusion: a rabbit model. Spine 1998;23:2276–81. [33] Spiro R, Pacetti S, Thompson A, et al. Evaluation of a new mineralized collagen bone grafting matrix in a long bone critical defect model. Paper presented at: 43rd Meeting of the Orthopaedic Research Society; February 9–11, 1997; San Francisco, CA. [34] Griffith S, Criscitello A, Cunningham B, et al. Non-human primate evaluation of an osteoconductive bone substitute in an interbody fusion cage. Paper presented at: EuroSpine; September 7–11, 1999; Munich, Germany. [35] Grosse S, Argenson C, Tavna A, et al. Mineralized collagen as a replacement for autogenous bone in posterolateral lumbar spinal fusion. Paper presented at: EuroSpine; September 7–11, 1999; Munich, Germany. [36] Lenke LG, Bridwell KH, Bullis D, et al. Results of in situ fusion for isthmic spondylolisthesis. J Spinal Disord 1992;5:433–42.
S.H. Kitchel / The Spine Journal 6 (2006) 405–412 [37] Resnick DK, Choudhri TF, Dailey AT, et al. Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 12: pedicle screw fixation as an adjunct to posterolateral fusion for low-back pain. J Neurosurg Spine 2005;2:700–6. [38] Kho VK, Chen WC. The results of posterolateral lumbar fusion with bone chips from laminectomy in patients with lumbar spondylolisthesis. J Chin Med Assoc 2004;67:575–8. [39] Ekman P, Moller H, Hedlund R. The long-term effect of posterolateral fusion in adult isthmic spondylolisthesis: a randomized controlled study. Spine J 2005;5:36–44. [40] Cammisa FP Jr, Lowery G, Garfin SR, et al. Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine fusion: a prospective controlled trial employing a sideby-side comparison in the same patient. Spine 2004;29:660–6. [41] Thalgott JS, Giuffre JM, Fritts K, et al. Instrumented posterolateral lumbar fusion using coralline hydroxyapatite with or without demineralized bone matrix, as an adjunct to autologous bone. Spine J 2001;1:131–7. [42] Madan SS, Harley JM, Boeree NR. Circumferential and posterolateral fusion for lumbar disc disease. Clin Orthop Relat Res 2003;409: 114–23. [43] Gehrchen PM, Dahl B, Katonis P, et al. No difference in clinical outcome after posterolateral lumbar fusion between patients with isthmic spondylolisthesis and those with degenerative disc disease using pedicle screw instrumentation: a comparative study of 112 patients with 4 years of follow-up. Eur Spine J 2002;11:423–7. [44] Kimura I, Shingu H, Murata M, et al. Lumbar posterolateral fusion alone or with transpedicular instrumentation in L4–L5 degenerative spondylolisthesis. J Spinal Disord 2001;14:301–10. [45] Hadley MN. Posterolateral fusion of the lumbar spine: rationale, indications, techniques, and results. Clin Neurosurg 2000;47: 483–94. [46] Gill K, O’Brien JP. Observations of resorption of the posterior lateral bone graft in combined anterior and posterior lumbar fusion. Spine 1993;18:1885–9.
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[47] Larsen JM, Rimoldi RL, Capen DA, et al. Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings. J Spinal Disord 1996;9:117–20. [48] Chafetz N, Cann CE, Morris JM, et al. Pseudarthrosis following lumbar fusion: detection by direct coronal CT scanning. Radiology 1987; 162:803–5. [49] Miyata S, Kambara K. [Bone union after lumbar postero-lateral fusion: comparative evaluation by x-ray and CT]. Nippon Seikeigeka Gakkai Zasshi 1994;68:1023–32. [50] Siambanes D, Mather S. Comparison of plain radiographs and CT scans in instrumented posterior lumbar interbody fusion. Orthopedics 1998;21:165–7. [51] Knop C, Bastian L, Lange U, et al. [Transpedicular fusion of the thoraco-lumbar junction. Clinical, radiographic and CT results]. Orthopade 1999;28:703–13. [52] Cook SD, Patron LP, Christakis PM, et al. Comparison of methods for determining the presence and extent of anterior lumbar interbody fusion. Spine 2004;29:1118–23. [53] Epstein NE, Silvergleide RS. Documenting fusion following anterior cervical surgery: a comparison of roentgenogram versus two-dimensional computed tomographic findings. J Spinal Disord Tech 2003; 16:243–7. [54] Santos ER, Goss DG, Morcom RK, et al. Radiologic assessment of interbody fusion using carbon fiber cages. Spine 2003;28:997–1001. [55] Shah RR, Mohammed S, Saifuddin A, et al. Comparison of plain radiographs with CT scan to evaluate interbody fusion following the use of titanium interbody cages and transpedicular instrumentation. Eur Spine J 2003;12:378–85. [56] Tullberg T, Brandt B, Rydberg J, et al. Fusion rate after posterior lumbar interbody fusion with carbon fiber implant: 1-year followup of 51 patients. Eur Spine J 1996;5:178–82. [57] Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am 1997;79:1699–709.
COMMENTARY Harvinder S. Sandhu, MD, MBA, New York, NY
The author has successfully described some, but not all, of the shortcomings of his prospective pilot trial evaluating the use of mineralized collagen and bone marrow aspirate (MC/BMA) for posterolateral spinal fusion. The study was designed to compare the use of MC/BMA for unilateral lumbar transverse process fusion with the use of iliac crest bone graft on the contralateral transverse processes in pedicle screw instrumented patients who were also receiving posterior lumbar interbody fusions with cages filled with iliac crest bone graft. Although the author is rightly concerned with his small sample size and the exclusion of subpopulations such as smokers, I am concerned with more fundamental issues such as study design and validity of conclusions. First, the experimental and control treatments are not independent and there is a likely bias toward equivalence. Disregarding the effect of the interbody intervention, one can speculate that the presence of a unilateral transverse process fusion, perhaps due to iliac crest grafting, will affect
the behavior on the opposite side. The effect may include resorption along the lateral portions of the inter-transverse space but also an increased probability of ankylosis along the facet joint. Indeed, the computed tomographic images provided in the article suggest just thatdfusion along the facet and pars rather than a frank bony bridge along the transverse processes. Second, the presence of a 360 intervention essentially delegates the biologically superior interbody space as the primary site for segmental arthrodesis. The immediate probable stress shielding of the posterior column caused by the interbody cage further diminishes the relevance of the biologic activity along the posterolateral gutters. The author’s explanation for confounding his study design with interbody fusion is that the procedure is customary in his practice. In my opinion, the conclusions of this paper would have been strengthened with a better study design. This is essentially a biologic study evaluating an alternative bone graft substitute for posterolateral lumbar fusion.