Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2 Assisted Spinal Interbody Fusion

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1 Musculoskeletal Imaging Original Research Sethi et al. Imaging fter Spinal Fusion Surgery Using rhmp-2 Musculoskeletal Imaging Original Research nil Sethi 1 Joseph Craig 2 Stephen artol 3 Wei Chen 4 Mark Jacobson 3 Chad Coe 3 Rahul Vaidya 1 Sethi, Craig J, artol S, et al. Keywords: bone morphogenetic protein, CT evaluation, radiographic features, rhmp-2, spinal fusion DOI: /JR Received ugust 12, 2010; accepted after revision December 15, Department of Orthopedics, Detroit Receiving Hospital, 4201 St. ntoine lvd, 4D-4, Detroit, MI ddress correspondence to. Sethi (anilsethi09@gmail.com). 2 Department of Radiology, Henry Ford Hospital, Detroit, MI. 3 Department of Orthopedics, Henry Ford Hospital, Detroit, MI. 4 iostatistics Core, Karmanos Cancer Institute and Wayne State University School of Medicine, Detroit, MI. CME This article is available for CME credit. See for more information. WE This is a Web exclusive article. JR 2011; 197:W128 W X/11/1971 W128 merican Roentgen Ray Society Radiographic and CT Evaluation of Recombinant Human one Morphogenetic Protein-2 ssisted Spinal Interbody Fusion OJECTIVE. one morphogenetic proteins MPs, when used in spinal fusion, hasten healing and initiate distinct imaging features. We undertook a study to record and analyze the radiographic and CT changes after the use of recombinant human bone morphogenetic protein 2 (rhmp-2) in spinal fusion surgery. MTERILS ND METHODS. This study included 95 patients who underwent spinal interbody fusion using rhmp-2. The lumbar spine fusion cohort consisted of 23 patients who underwent anterior lumbar interbody fusion, 36 patients who underwent transforaminal lumbar interbody fusion, and two patients who underwent posterior lumbar interbody fusion. The remaining 34 patients underwent anterior cervical decompression and fusion. RESULTS. polyetheretherketone cage was used as an interbody spacer in 59 patients (82 levels) and an allograft bone was the spacer in 36 patients (55 levels). Patients were evaluated 2 and 6 weeks after the procedure and then 3, 6, 12, and 24 months after the procedure. ll patients underwent radiography at every follow-up visit, and CT evaluation was performed in 32 patients. CONCLUSION. Features observed on imaging that we attributed to the use of rhmp-2 included an enhanced fusion rate and an increased incidence of prevertebral soft-tissue swelling in patients who underwent cervical fusion. Endplate resorption was observed in 100% of patients who underwent cervical fusion and in 82% of the lumbar levels. Subsidence of the cage resulting in narrowing of the disk space was seen in more than 50% of cases. Cage migration and heterotopic bone formation in the spinal canal and neural foramen occurred maximally in the lumbar spine of patients in whom a polyetheretherketone cage was placed using a transforaminal approach. S pinal fusion is commonly performed for restoring spinal stability after surgery for degenerative disease, spondylolisthesis, deformity correction, and trauma. utografts as well as allografts have been used to promote fusion. However, with advancements in the use of bone substitutes for spine fusion, bone morphogenetic proteins (MPs) have been reported to be successful in inducing bone growth with an efficacy equivalent to or even greater than autograft [1, 2]. Marshall Urist first reported on the ability of MPs to form bone by autoinduction [3]. MPs are released by platelets and osteoprogenitor cells and stimulate cellular proliferation, angiogenesis, osteoblast differentiation, and direct bone matrix formation [4]. With the use of recombinant technology, MP is now manufactured in abundant quantities. The use of recombinant human MPs (rh- MPs) has been approved by the U.S. Food and Drug dministration for anterior fusion of the lumbar spine in skeletally mature patients, for treatment of open tibial shaft fractures, and for certain oral and maxillofacial uses [5]. Encouraged by the success of procedures performed using a MP, surgeons have expanded its use to other spinal fusion techniques [6 10]. When used in spinal fusion, MP hastens healing and initiates distinct radiographic changes [2, 6]. With the extensive use of MP, it is now being seen more often in everyday radiologic practice. Radiographs and CT scans are commonly used for the evaluation of fusion in the postoperative spine. MRI may be a useful adjunct, but MRI of the postoperative spine is vulnerable to metal-induced artifacts. For an accurate postoperative assessment of spinal fusion, familiarity with the imaging appearance of the lumbar spine after the use of MP is imperative. lthough there are extensive data in the literature on the clinical W128 JR:197, July 2011

2 Imaging fter Spinal Fusion Surgery Using rhmp-2 outcomes of spinal fusion with the use of MP [2, 7 9], radiographic data about its use are sparse. Interbody cages permit maintaining disk and foraminal height. The cages may be made of titanium, polyetheretherketone, carbon fiber, or allograft bone. The radiolucent polyetheretherketone cage and allograft bone allow a clearer, unobstructed radiographic view of new bone formation during followup examinations [11 14] and are ideal spacers to study the imaging cascade of changes. We undertook this study to analyze and record the radiographic findings after spinal fusion surgery using rhmp-2 and allograft and polyetheretherketone cages. Materials and Methods This study was approved by the institutional review board and included 95 patients who underwent spinal interbody fusion surgery between ugust 2003 and November 2005 in which rhmp-2 was used. Sixty-one patients underwent lumbar interbody fusion, and 34 patients underwent anterior cervical decompression and fusion. The study group included 52 men and 43 women who ranged in age from 18 to 79 years; the average age at the time of surgery was 51 years. Treatment consisted of single or multiple levels of fusion in the cervical and lumbar spine, resulting in a total of 50 fusion levels in the cervical spine and 87 levels in the lumbar spine. The distribution of the 61 patients who underwent lumbar fusion consisted of 23 patients who underwent anterior lumbar interbody fusion (LIF), 36 patients who underwent transforaminal lumbar interbody fusion, and two patients who underwent posterior lumbar interbody fusion. ll cervical fusion patients underwent anterior cervical decompression and fusion with an anterior stabilizing plate. polyetheretherketone cage was used as an interbody spacer in 59 patients (82 levels), whereas allograft bone was the spacer in the remaining 36 patients (55 levels). Fusion was assisted with rhmp-2 in every patient. Patients were reviewed 2 and 6 weeks and 3, 6, 12, and 24 months after surgery. Radiologic assessment included radiography in all patients at every follow-up visit and CT evaluation in 32 patients for assessment of persistent or recurring back or leg pain. Radiographic images were examined for new bone formation, endplate resorption, subsidence of the interbody disk space, and migration of the cage. In patients who underwent anterior cervical fusion, the space anterior to the vertebral body was also measured. Characterization of new bone within the interbody disk space was recorded as no bone formation, visible new bone formation, possible fusion, or probable fusion. Endplate resorption was classified as no resorption, mild resorption, moderate resorption, or severe resorption [11]. Disk height was measured before and after surgery to record subsidence, and the measurements were compared with a standard object for each patient and expressed as a ratio. comparison of ratios was performed on follow-up radiographs. These measurements were compared with measurements from CT scans and were found to vary by approximately 1 mm. We thus considered any subsidence of less than 10% to be insignificant [15]. Quantitative assessment of any movement of the cage was characterized as mild, moderate, or severe. The direction of cage migration was also noted. Soft-tissue swelling anterior to the vertebral body was measured at C3 and C6 as a digital line measurement from the front of the vertebral body to the edge of the soft-tissue shadow. This measurement was standardized by the size of the plate and has been described by our group in another report as follows [11]: soft-tissue swelling in millimeters (mm) measured plate size divided by original plate size = mm of swelling. Radiographic measurements were made by three independent observers on the electronic public access computer system (EPCS, Stentor). The Fisher exact test was used for comparing proportions in two independent populations. two-sided test with a significance level of 0.05 was used. p value of < 0.05 was considered significant without multiple testing adjustment. ll analyses were carried out using statistical software (R version 2.9.2, The R Project for Statistical Computing). Results New bone formation within the interbody disk space was recorded. ecause patients were not reexplored at the endpoint and outcomes of fusion were primarily assessed with radiographs, an endpoint with the term probable fusion was used. Probable fusion was defined as the presence of bridging bone in or around the cage. In the cervical spine, 21 of 23 cases with a polyetheretherketone cage showed an appreciable amount of new bone formation by 6 months after surgery, with all showing possible or probable fusion at 9 months after surgery (Fig. 1). Radiographic evidence of new bone formation in the lumbar spine with a polyetheretherketone cage was observed in 20 of 36 patients by 6 months after surgery, 30 of 36 patients at 9 months, and all 36 patients at 1 year. The appearance of bone in the lumbar spine was delayed compared with the cervical spine. In patients with allograft bone as a spacer, the earliest evidence of new bone formation in the cervical spine was seen at 3 months after surgery (Fig. 2). Nine of 11 patients with an allograft spacer showed appreciable new bone at 6 months. In the lumbar spine, the fusion process was visible radiologically at 6 months in 22 of 25 patients with an allograft spacer, and all patients showed fusion at 1 year (Fig. 3). The Fisher exact test revealed that there was a statistically significant difference (p = 0.004) in the speed of fusion at 6 months after surgery at the cervical spine and at the lumbar spine, with cervical fusion noted to occur at a more rapid pace. The speed of fusion at the cervical spine and the speed of fusion at the lumbar spine were not statistically different at 9 months (p = 0.07). The incidence of endplate resorption was 100% in the cervical spine. During this phase, we also noted osteolysis of the vertebral body presenting as bony defects (Fig. 3) in some patients. lthough resorption was seen 2 weeks after surgery in a few patients, all patients experienced some form of resorption by 6 weeks (Fig. 4). The largest transition between resorption and new bone formation occurred between 3 and 6 months after surgery. The lumbar vertebrae showed a later onset of resorption. dditionally, 18% of the lumbar levels displayed no radiographically detectable endplate resorption. The rate of resorption was variable and the same patient showed resorp- Fig. 1 Serial radiographs of 34-year-old man who underwent spinal fusion surgery show progression of fusion in cervical spine. JR:197, July 2011 W129

3 Sethi et al. Percentage of Cases Little or no resorption Mild resorption Moderate resorption Severe resorption 0.5 Mild regrowth Moderate regrowth Full regrowth Time fter Surgery (mo) Fig. 2 Schematic shows bone resorption and bone formation timeline in cervical spine after spinal fusion surgery with recombinant human bone morphogenetic protein 2. Fig. 3 CT evaluation of patients who underwent spinal fusion with recombinant human bone morphogenetic protein 2., CT scan confirms fusion in 44-year-old woman., CT scan shows evidence of vertebral osteolysis (arrow) in 52-year-old woman. Fig year-old man who underwent spinal fusion surgery with recombinant human bone morphogenetic protein 2., Radiograph obtained immediately after surgery., Radiograph obtained 1.5 months after surgery shows evidence of endplate resorption. tion in different stages at different fusion levels. Superior images of endplate resorption and osteolysis were noted on CT. The largest transition from resorption to bone formation occurred between 6 and 9 months after surgery in the lumbar spine. The percentage of endplate resorption in 2 6 weeks was statistically higher in the cervical spine than in the lumbar spine, with a p value of Subsidence was obvious on radiographs in more than 50% of the cases at 3 months after surgery. Radiographically subsidence presents as narrowing of the disk space (Fig. 5) and clinically causes reduction of the area of the intervertebral foramen with the possibility of nerve root entrapment. Subsidence was noted to occur between 6 weeks and 3 months after surgery, and there was no significant subsidence at 6 months. For the entire study group, the average subsidence, or narrowing of the disk space, at 12 months was 16.5% (SE, 2.5%; range, 0 58%) with p < CT scans of 32 patients were obtained during the follow-up period. The scans revealed two phenomena that may have contributed to subsidence. The first was an early turnover and incorporation of the allograft, likely causing a loss of structural support. The second was endplate erosion, which was seen in all the allograft rhmp-2 cases that were scanned. Heterotopic bone formation in the spinal canal and intervertebral foramen was another feature noted with the use of rhmp-2 and was commonly seen in patients who underwent interbody fusion using the transforaminal approach. Patients typically reported recurrence of leg pain 6 8 weeks after surgery after an initial symptom-free period. CT of the lumbar spine revealed the presence of heterotopic bone in the spinal canal or neural foramen in these patients (Fig. 6), and these findings were confirmed on revision surgery. In patients who underwent a cervical fusion, lateral digital radiographs were measured for prevertebral distention at several time points (Fig. 7). The preoperative value at C3 was measured as 5.0 ± 1.7 mm (mean ± SD). ll patients had prevertebral distention of the soft tissue during the postoperative period. Prevertebral swelling at C3 measured 15.7 ± 7.8 mm at 1 week, 11.8 ± 3.7 mm at 2 weeks, and 8.0 ± 3.1 mm at 6 weeks. There was a significant difference in prevertebral swelling at various time points during the first 6 weeks; after that, the swelling returned to near preoperative values. There was no signif- W130 JR:197, July 2011

4 Imaging fter Spinal Fusion Surgery Using rhmp-2 icant difference in prevertebral swelling when measured at the C6 level. Cage migration was observed to occur maximally in patients who underwent interbody fusion using the transforaminal approach with the polyetheretherketone cage (Fig. 8). This complication was observed in 10 of 26 patients who underwent transforaminal lumbar interbody fusion using a polyetheretherketone cage. In the cervical spine patients and remaining lumbar spine patients who underwent anterior fusion, one patient each displayed minimal migration of the cage with no clinical symptoms. Cage migration was not observed in Fig year-old woman who underwent spinal fusion surgery with recombinant human bone morphogenetic protein 2. and, Radiographs show increased bending of anterior plate (arrow) in lumbar spine signifying subsidence. Fig. 6 CT myelography of 40-year-old man who underwent spinal fusion surgery with recombinant human bone morphogenetic protein 2. and, Images show heterotopic bone (arrows, ) in spinal canal and right neural foramen. patients who had allograft bone as a spacer. The difference in the incidence of cage migration with the use of the transforaminal lumbar interbody fusion technique was noted to be statistically significant for polyetheretherketone cages versus allograft (p < 0.001). Furthermore, there was a statistically significant difference (p = 0.038) in the occurrence of cage migration in transforaminal lumbar interbody fusion versus LIF. Similarly, a statistically significant difference was noted (p = 0.007) in the occurrence of cage migration in transforaminal lumbar interbody fusion versus anterior cervical decompression and fusion. Discussion In the United States, rhmp-2 is commercially available as INFUSE one Graft (Medtronic Sofamor Danek). Graft sizes range from 0.7 to 8 cm 3 containing mg of rhmp-2 powder. The protein is delivered on an absorbable collagen sponge available in a range of sizes from to 3 4 inches (from to cm). The sponge functions to provide scaffolding on which new bone formation can occur and to retain MP at the site of implantation. During application, the rhmp-2 powder is mixed with sterile water and is then applied to the collagen sponge. The sponges may be inserted inside a cage or placed around a cage in the disk space. Depending on the fusion technique used, the sponges may also be placed on the posterior elements or in the posterolateral gutter bridging the transverse processes. The biologic response to MP-2 is probably related to dose; however, the optimal dose is not known. Patients in this study received 2 mg per level in the lumbar spine and 1 mg per level in the cervical spine. Recent studies conducted using rhmp-2 have yielded promising results, suggesting that rhmp-2 can augment spinal fusions [7, 16, 17]. Interbody cages supplemented with the protein are also known to enhance fusion [2, 6]. lthough the percentage of successful fusion rates increased with the use of MP, minimal radiographic data documenting the bone healing process are available. Many studies involving spinal fusion in hu- Fig year-old woman who underwent spinal fusion surgery with recombinant human bone morphogenetic protein 2. Radiograph shows measurement (lines) of prevertebral space in cervical spine at C3 and C6. JR:197, July 2011 W131

5 Sethi et al. Fig year-old man who underwent spinal fusion surgery with recombinant human bone morphogenetic protein 2., Radiograph obtained 0.5 month after surgery shows polyetheretherketone cage (arrow)., Radiograph obtained 3 months after surgery shows cage (arrow) has migrated. Patient underwent revision surgery and good fusion was noted. Polyetheretherketone cage did not move and had to be burred down flush with posterior vertebral border. mans have been performed using radiopaque cages that limit the potential to observe the fusion process [6, 16, 18 20]. In this study, we examined 95 spinal fusions performed using rhmp-2 with allograft and with polyetheretherketone cages. The use of the radiotranslucent polyetheretherketone cages allowed radiographic analysis of the changes occurring over the span of 1 year. Prevertebral Swelling ll patients who underwent anterior cervical fusion displayed some degree of prevertebral swelling. However, as we reported previously [15], patients with MP-assisted fusion show an enhanced inflammatory phase that results in greater prevertebral swelling. The presence of prevertebral swelling with haziness of the endplates on radiography mimics infection. In one of our earliest cases, an increase in the soft-tissue space anterior to the vertebrae associated with difficulty in swallowing led to reoperation during the first postoperative week. wound infection was suspected and the patient was reexplored. However, there was no evidence of infection at surgery. Edematous tissue was seen, cultures of which were reported sterile. In-hospital monitoring led to an improvement in the patient s symptoms. Differentiation of infection from MP-induced inflammation remains difficult. efore we make a diagnosis of infection, we look for fever and other parameters that include WC count, erythrocyte sedimentation rate, and C-reactive protein level. However, as experienced physicians are aware, the elevation of these parameters in a postoperative patient does not necessarily denote infection. Prevertebral swelling after the use of MP usually returns to normal 6 weeks after surgery. Fusion Rate In numerous studies, investigators have reported an accelerated rate of fusion with MP. In an earlier report [15], we observed radiologic signs of fusion at an average of 6 months after surgery with the use of rhmp-2. In comparison, patients without MP showed fusion at an average of 19 months after surgery [15]. In this study, the radiolucency of the polyetheretherketone cages enabled us to observe the radiographic process of healing. New bone formation was not visible until 43 days postoperatively in most cases and later in others. The transition from bone resorption to new bone formation occurred between 12 and 24 weeks after surgery in the cervical spine and between 24 and 36 weeks in the lumbar spine. Radiographic evidence of this stage is probably delayed from the actual process because on reexploration for recurrence of leg pain, it was observed that the cage was solidly fused by 8 12 weeks. Endplate Resorption n interesting characteristic was seen during the progression of fusion: We found that there was endplate resorption in 100% of the levels with the use of rhmp-2. This phenomenon was first noted at 1.5 months postoperatively and lasted until 6 months. In some patients, endplate resorption was associated with osteolysis seen on imaging studies as lytic lesions in the vertebral body (Fig. 3). Subsidence MP causes the interbody cage to subside, resulting in narrowing of the disk space. This phenomenon was observed with the use of both the allograft and polyetheretherketone cages. The incidence of subsidence was greater in patients who underwent fusion of the cervical spine as compared with those who underwent fusion of the lumbar spine. However, the average amount of subsidence was greater in the lumbar spine patients. Subsidence may be attributed to the resorption of endplates, allowing penetration of the cage into the vertebral body. No significant degree of subsidence was observed 6 months after surgery. Cage Migration Endplate resorption caused loosening of the cage that then became at risk for migration. The polyetheretherketone cage was more prone to migration than the allograft spacer. Cage migration was not observed at 6 months after surgery when new bone was visible on radiographs. ll cages in our series were supplemented with an anterior locking plate in the cervical spine and anterior buttress plates in anterior lumbar fusions. ll lumbar surgeries had posterior constructs as well. Despite adequate stabilization of the cage, migration could not be prevented because of the lysis associated with the use of MP. Heterotopic one MP is also known to cause bone formation at heterotopic sites including the spinal canal and neural foramen. In a recent report [21], the use of rhmp-2 was associated with a 21% rate of heterotopic bone formation. This included a case in which almost 75% of the neural foramen was ossified [21]. In an earlier study, we reported on the presence of heterotopic bone formation in the neural foramen in patients who underwent revision surgery; we postulated that the predominance of cases of cage migration in patients with transforaminal and posterior access to the disk space is possibly because of the site of insertion of the cage and the fact that there was no barrier to extrusion as in the anterior cases [11]. Hence, in patients with recur- W132 JR:197, July 2011

6 Imaging fter Spinal Fusion Surgery Using rhmp-2 rence of pain, the presence of new bone in the spinal canal and neural foramen needs to be evaluated on imaging studies (Fig. 7). Conclusion This study analyzes the radiographic effects of MP on spinal fusion. lthough MP accelerates the rate of interbody spinal fusion, it also produces a marked inflammatory response. This response is expressed radiographically as increased prevertebral swelling in patients who undergo cervical fusion. MP also causes endplate resorption, subsidence, and an increase in the incidence of cage migration. References 1. Cheng H, Jiang W, Phillips FM, et al. Osteogenic activity of fourteen types of human bone morphogenetic proteins (MPs). J one Joint Surg m 2003; 85: Mummaneni PV, Pan J, Haid RW, Rodts GE. Contribution of recombinant human bone morphogenetic protein-2 to the rapid creation of interbody fusion when used in transforaminal lumbar interbody fusion: a preliminary report. J Neurosurg Spine 2004; 1: Urist MR. one: formation by autoinduction. Science 1965; 150: Valdes M, Thakur N, Namdari S, Ciombor DM, Palumbo M. Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review. rch Orthop Trauma Surg 2009; 129: ; Epub 2009 Mar U.S. Food and Drug dministration, Center for Devices and Radiological Health Website. FD public health notification: life-threatening complications associated with recombinant human bone morphogenetic protein in cervical spine fusion fda-infuse.pdf. Published July 1, ccessed November 29, Sandhu HS. one morphogenetic proteins and spinal surgery. Spine (Phila Pa 1976) 2003; 28(suppl):S64 S73 7. urkus JK, Transfeldt EE, Kitchel SH, Watkins RG, alderston R. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 2002; 27: oden SD, Kang J, Sandhu HS, Heller JG. Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial 2002 Volvo award in clinical studies. Spine (Phila Pa 1976) 2002; 27: Valentic-Opran, Wozney J, Csimma C, et al. Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop Relat Res 2002; 395: Einhorn T. Clinical applications of recombinant human MPs: early experience and future development. J one Joint Surg m 2003; 85(suppl 3): Vaidya R, Sethi, artol S, Jacobson M, Coe C, Craig JG. Complications in the use of rhmp-2 in PEEK cages for interbody spinal fusions. J Spinal Disord Tech 2008; 21: Matge G. Cervical cage fusion with 5 different implants: 250 cases. cta Neurochir (Wien) 2002; 144: oakye M, Mummaneni PV, Garrett M, Rodts G, Haid R. nterior cervical discectomy and fusion FOR YOUR INFORMTION This article is available for CME credit. See for more information. involving a polyetheretherketone spacer and bone morphogenetic protein. J Neurosurg Spine 2005; 2: Toth JM, Wang M, Estes T, Scifert JL, Seim H III, Turner S. iomaterials 2006; 27: Vaidya R, Weir R, Sethi, Meisterling S, Hakeos W, Wybo CD. Interbody fusion with allograft and rhmp-2 leads to consistent fusion but early subsidence. J one Joint Surg r 2007; 89: askin DS, Ryan P, Sonntag V, Westmark R, Widmayer M. prospective, randomized controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the T- LNTIS anterior cervical plate. Spine (Phila Pa 1976) 2003; 28: ; discussion, urkus JK, Sandhu HS, Gornet MF, Longley MC. Use of rhmp-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spine surgery. J one Joint Surg m 2005; 87: Jassen ME, Lam C, eckham R. Outcomes of allogenic cages in anterior and posterior lumbar interbody fusion. Eur Spine J 2001; 10(suppl 2): S158 S urkus JK. one morphogenetic proteins in anterior lumbar interbody fusion: old techniques and new technologies. J Neurosurg Spine 2004; 3: Kleeman TJ, Michael hn U, Talbot-Kleeman. Laparoscopic anterior lumbar interbody fusion with rhmp-2: a prospective study of clinical and radiographic outcomes. Spine (Phila Pa 1976) 2001; 26: Joseph V, Rampersaud YR. Heterotopic bone formation with the use of rhmp2 in posterior minimal access interbody fusion: a CT analysis. Spine (Phila Pa 1976) 2007; 32: JR:197, July 2011 W133