Abstract
Study Design/Setting
Randomized, controlled study in a laboratory setting. Blinded observations/assessment of study outcomes.
Objective
The purpose of this study is to determine the performance characteristics of PROGENIX® DBM putty as a bone graft extender, enhancer, and substitute in a rabbit posterolateral spine fusion model.
Summary of Background Data
The rabbit posterolateral fusion model is an established environment for testing of fusion concepts. It offers the opportunity to obtain radiographic, histological, and biomechanical data on novel fusion materials.
Methods
Forty rabbits were entered into the study with 37 used for analysis. Bilateral posterolateral lumbar intertransverse fusions were performed at L5-L6. the lateral two thirds of the transverse processes were decorticated and covered with graft material: autograft only (1.5 or 3.0 cc/side), a combination of PROGENIX® (1.5cc) + autograft (1.5cc), PROGENIX® (1.5cc) + autograft (3.0cc), or PROGENIX® only (3.0cc/side).
Results
Radiographic Fusion: At 8 weeks the 3.0cc autograft group had a 67% fusion rate and the 1.5cc autograft group fused in 25%. the extender group (1.5cc autograft + 1.5cc PROGENIX®) had an 88% fusion rate at 8 weeks. In the enhancer group (3.0 cc autograft + 1.5cc PROGENIX®) 86% of the spines were fused. the substitute group (PROGENIX® only) had a fusion rate of 38%. Manual Palpation: the 3.0cc autograft group had a 67% fusion rate and the 1.5cc autograft group fused in 38%. the extender group had an 88% fusion rate. In the enhancer group 86% of the specimens fused. the substitute group had a 50% fusion rate.
Conclusions
In a rabbit posterolateral fusion model, PROGENIX® DBM Putty in an autograft extender or enhancer mode produced manual palpation and radiographic fusion rates equivalent or slightly better than autograft fusion (3cc) alone. the results from the two autograft groups demonstrate the need for adequate graft volume to achieve high radiographic and mechanical fusion rates.
Introduction
Iliac crest autograft is considered the gold standard graft material despite limitations in the quantity available and complications associated with the harvesting procedure1-12. These disadvantages have motivated clinicians and investigators to seek alternative graft materials to extend, enhance and/or substitute for autograft. Examples of such alternatives include: allografts, synthetic materials and recombinant human bone morphogenetic proteins (BMPs).
Many such products have been in clinical use in various forms for a number of years. Evidence for methods of use, appropriate volume/percentages of graft material, and local biocompability/fusion has sometimes been lacking despite incorporation of these technologies into clinical practice. As more technologies become available, scientific investigations have the opportunity to contribute to the understanding of efficacious and safe use.
The current study was performed to assess a demineralized bone matrix (DBM)-based graft material (PROGENIX® DBM Putty) as an autograft extender, enhancer, and substitute in the rabbit posterolateral fusion model. Fusion rates of iliac crest autograft in two separate volume-based groups were compared to lesser amounts of autograft extended or enhanced with the investigational material and the investigational material alone.
Purpose
The purpose of this study was to determine the performance characteristics of PROGENIX® DBM putty (Spinal Graft Technologies) as a bone graft extender, enhancer, and substitute in a rabbit bilateral posterolateral spine fusion model.
Materials and Methods
Skeletally mature New Zealand White Rabbits weighing 4.5-5.5 kg were obtained from Myrtal Rabbitry (Thompson, TN) and entered into the study. All procedures were approved by the Institutional Animal Care Use Committee (#0612251) and conducted at the Bone Healing Research Lab, Iowa Spine Research Center. Throughout the study, animals were individually caged and monitored daily for signs of pain and discomfort.
The test article used in this study was PROGENIX® Putty in which the human DBM (demineralized bone matrix) component was replaced by rabbit DBM. This was done to avoid the potential for cross-species incompatibility. The procedures used for preparation of this material modeled the clinical manufacturing process. The alginate, collagen and PBS (phosphate buffered saline) were identical to those used in the clinical product.
A single level posterolateral intertransverse process fusion was performed in 40 rabbits (Table 1), bilaterally at L5-L6, with autogenous bone graft (3.0cc or 1.5cc/ side) from the iliac crest, PROGENIX® DBM putty (3.0cc/side), or a combination of PROGENIX® DBM putty + autograft. The PROGENIX® DBM Putty + autograft combination groups were either 3.0cc autograft + 1.5cc PROGENIX® (enhancer) (4.5 cc / side), or 1.5cc autograft + 1.5cc PROGENIX® (extender) (3.0cc / side).
Table 1.
Experimental Design
| Group | Graft type | Manual Palpation n= |
X-ray (3,6wk) n= |
Histology n= |
Sacrifice |
|---|---|---|---|---|---|
| Group 1 | PROGENIX® DBM Putty alone (3cc)[substitute] | 8 | 8 | 4 | 8 Weeks |
| Group 2 | PROGENIX® DBM Putty (1.5cc) + 3cc autograft [enhancer] | 8 | 8 | 4 | 8 Weeks |
| Group 3 | PROGENIX® DBM Putty 1.5cc + 1.5cc autograft[extender] | 8 | 8 | 4 | 8 Weeks |
| Group 4 | autograft 3cc [autograft control] | 8 | 8 | 4 | 8 Weeks |
| Group 5 | autograft 1.5cc [control for extender quantity] | 8 | 8 | 4 | 8 Weeks |
Surgical Procedure
All operative procedures were performed in a surgical suite using inhalation anesthesia and aseptic techniques. A preanesthetic dose of Ketamine HCL 26mg/kg, Acepromazine Maleate 0.15mg/kg, and Xylazine HCL 0.78 mg/kg was administered intramuscularly. Surgical anesthesia was maintained with 1.5–2.5% isoflurane delivered in O2. Cardiorespiratory monitoring was continued throughout the procedure.
A parenteral dose of cefazolin (13 mg/kg) was administered for infection prophylaxis preoperatively and then BID for 48 hours post-op.
Rabbits were placed prone on the operating table and surgically prepped with 70% Betadine solution. A dorsal midline incision, approximately 15 centimeters long, was made from L1 to the sacrum. A full-thickness flap of skin and subcutaneous tissue was developed
and retracted on both sides. Approximately 1.5–2.0 cm lateral to the midline at the L5–L6 level, a 4- to 6-cm longitudinal incision was made through the lumbar fascia. Through the fascial incision, the iliocostalis muscle was divided exposing the underlying longissimus muscle. The transverse processes were exposed through blunt dissection along the lateral border of the longissimus muscle. A small self-retaining retractor was used to maintain exposure of the two transverse processes and the intertransverse ligament.
The surgical sites were packed with gauze after completing the surgical approach. After exposure and packing of the contralateral fusion site, small self-retaining retractors were placed in the surgical site to allow exposure for the decortication of the transverse processes. Decortication of the fusion site was performed with a high-speed 3.0mm round burr. Decortication was performed only until bleeding bone was achieved and was limited to the lateral transverse processes with no decortication of the medial boney structures. This technique has previously been validated to provide autograft fusions in approximately 50–70% of animals when using 3.0cc of autograft per side. This provides a challenging model and allows for comparison of test articles to autograft.
Approximately 3.0 cc of corticocancellous bone graft from each iliac crest was obtained as needed depending on randomization – a volume considered to be the maximum amount which can be harvested from the rabbit iliac crest without significant animal morbidity13-18. The morselized cancellous bone graft, PROGENIX® DBM putty, or the combination of PROGENIX® DBM Putty + autograft was placed between the transverse processes in the paraspinal bed. Fascia and skin were closed with 3–0 Vicryl and then the skin was stapled with 35W surgical staples. Butorphanol (1–7.5 mg/kg IM q4) and Flunixin Meglumine (1.1mg/kg IM q12) were given daily for 48 hours post-op.
All the rabbits were radiographed at 3, 4 and 8 weeks post-operatively. Animals were humanely euthanized at 8 weeks post surgery, a time point consistent with the published literature of this model16;18–22. Following necropsy, high resolution Faxitron radiographs were obtained of the explanted spines. A random specimen from each group was also subjected to 3D computerized tomography (CT).
Three (3) rabbits were omitted from the study due to post-op complications (2 Pasteurella infections and 1 GI inflammation). Two of the animals were in Group 4 (resulting in n=6), and 1 in Group 2 (n=7). This finding supports prior evidence that harvesting the full autograft volume of 3cc's from both iliac crests has significant mortality.
Results
Radiographic
Radiographic fusion (Figure 1) was judged by continuous trabecular continuity between the affected transverse processes. At least one side of the spine had to have continuous bridging bone between the transverse processes to be classified as fused.
Figure 1. 8 Week Faxitron X-Ray and 3D CT.
At 8 weeks the 3.0cc autograft group had a 67% fusion rate (4/6) and the 1.5cc autograft group fused in 25% (2/8) of the rabbits. In the enhancer group (3.0 cc autograft + 1.5cc PROGENIX®), 85% (6/7) of the spines were fused. The extender group (1.5cc autograft + 1.5cc PROGENIX®) had an 88% (7/8) fusion rate at 8 weeks. The substitute group (PROGENIX® only) had a radiographic fusion rate of (38%, 3/8). Individual results are listed in the Table 2.
Table 2.
Faxitron radiographic results
| Animal # | Group | Radiographic Fusion | Manual Palpation Fusion |
|---|---|---|---|
| 1 | 1 | Pseudarthrosis | Not Solid |
| 2 | 1 | Fused | Solid |
| 3 | 1 | Pseudarthrosis | Not Solid |
| 4 | 1 | Pseudarthrosis | Not Solid |
| 5 | 1 | Pseudarthrosis | Not Solid |
| 6 | 1 | Pseudarthrosis | Solid |
| 7 | 1 | Fused | Solid |
| 8 | 1 | Fused | Solid |
| 9 | 2 | Fused | Solid |
| 10 | 2 | Fused | Solid |
| 11 | 2 | Pseudarthrosis | Not Solid |
| 12 | 2 | Fused | Solid |
| 13 | 2 | Fused | Solid |
| 14 | 2 | Fused | Solid |
| 15 | 2 | Fused | Solid |
| 16 | 3 | Fused | Solid |
| 17 | 3 | Pseudarthrosis | Solid |
| 18 | 3 | Fused | Solid |
| 19 | 3 | Fused | Solid |
| 20 | 3 | Fused | Not Solid |
| 21 | 3 | Fused | Solid |
| 22 | 3 | Fused | Solid |
| 23 | 3 | Fused | Solid |
| 24 | 4 | Fused | Solid |
| 25 | 4 | Pseudarthrosis | Not Solid |
| 26 | 4 | Fused | Solid |
| 27 | 4 | Fused | Solid |
| 28 | 4 | Fused | Solid |
| 29 | 4 | Pseudarthrosis | Not Solid |
| 30 | 5 | Fused | Solid |
| 31 | 5 | Pseudarthrosis | Not Solid |
| 32 | 5 | Pseudarthrosis | Not Solid |
| 33 | 5 | Pseudarthrosis | Solid |
| 34 | 5 | Pseudarthrosis | Not Solid |
| 35 | 5 | Fused | Solid |
| 36 | 5 | Pseudarthrosis | Not Solid |
| 37 | 5 | Pseudarthrosis | Not Solid |
3D-CT
Computerized tomography (CT) images were obtained from one animal from each group for investigator's use as a possible imaging tool to determine fusion across the transverse processes (Figure 1). No qualitative or quantitative analyses were performed with these images. Therefore, CT images in this manuscript are only a visual tool to see the graft characteristics (size, shape, etc.) in a limited number of animals.
Manual Palpation
Stiffness of the fused motion segment was assessed by manual palpation13. The fusion was graded by three independent blinded observers as “solid” if no detectable motion at the disc space was detected in flexion and extension. The fusion was graded as “not solid” if motion was present. Final results were determined by agreement of at least 2 of the 3 observers.
The 3.0cc autograft group had a 67% fusion rate (4/6) and the 1.5cc autograft group fused in 38% (3/8) of the rabbits. In the enhancer group (3.0 cc autograft + 1.5cc PROGENIX®), 86% (6/7) of the spine were fused. The extender group (1.5cc autograft + 1.5cc PROGENIX®) had a 88% (7/8) fusion rate. The PROGENIX® only group (substitute) had a 50%, (4/8) fusion rate when tested mechanically.
Manual palpation results (Table 2) correlated with the radiographic assessment with the exception of 1 animal from the PROGENIX® alone group and 1 from the 1.5 cc autograft group. In each of these groups, no motion was evident by manual palpation although they were graded as ‘not fused’ radiographically.
Histology (Figure 2)
Figure 2. Histology Examples Photomicrographs (50µm section @ 1X) of Group 1-PROGENIX® Putty (3.0cc/side), Group 2-PROGENIX® Putty (1.5cc/side) + Autograph (3.0cc/side), Group 3-PROGENIX® Putty (1.5cc/side) + autograph (1.5cc/side), Group 4- Autograph (3.0cc/side), and Group 5- Autograph (1.5cc/side).
There were no adverse inflammatory reactions to the PROGENIX® DBM Putty regardless of volume of test article. The PROGENIX® DBM Putty treatment groups tended to have more histological evidence of mature/immature bone development across the inter-transverse process spaces than did the autograft controls. In all groups except the 1.5cc/side autograft, most new bone growth was regularly seen adjacent to the transverse processes and variably extended across intertransverse process space.
These results suggest that treatment groups had enhanced bone formation and fusion over the control groups. Results also demonstrated that the PROGENIX® Putty material was remodeled into host bone with little residual graft material remaining after 8 weeks. The extent of remodeling also was greater than that observed for the autograft, likely due to the difference between the mineral content of the materials (autograft is mineralized whereas PROGENIX® Putty is composed primarily of demineralized bone).
Discussion
This study demonstrates the efficacy of PROGENIX® DBM Putty in separate autograft extender/enhancer applications and as a stand-alone bone graft substitute in a rabbit model (Table 3). Similar models have been used to verify autograft extenders/enhancers with reproducible results. The manual palpation fusion rate of 67% observed in the autograft control group is consistent with the rate demonstrated in prior studies performed in this laboratory as well as other published studies13;23–27. PROGENIX® DBM Putty + autograft, regardless of concentration of autograft, demonstrated increased fusion rates compared to the autograft controls. The ability of the PROGENIX® DBM Putty to homogenously mix with the morselized autograft allowed a continuous mixture of substrate with minimal void within the graft site for new bone to develop and fuse the motion segment.
Table 3.
Summary of Results
| Group | Test Article | Radiographic Fusion | Manual Palpation |
|---|---|---|---|
| 1 | PROGENIX® Putty 3cc (Substitute) | 38% | 50% |
| 2 | PROGENIX® Putty 1.5cc + Auto 3.0cc (Enhancer) | 86% | 86% |
| 3 | PROGENIX® Putty 1.5cc + Auto 1.5cc (Extender) | 87% | 87% |
| 4 | Autograft 3cc (Control) | 67% | 67% |
| 5 | Autograft 1.5cc (Control for Extender Group) | 25% | 38% |
The results from the autograft groups also demonstrate the need for adequate graft volume to achieve increased fusion rates in this model, confirming a concept that has been previously proposed to affect fusion rates in the rabbit model22. When 3cc was used 67% fused, whereas 1.5cc resulted in only 25% radiographic and 38% palpation fusions. This is good evidence of why the need for graft extenders is important - as autograft availability is limited and harvesting is associated with morbidity, increased operative time and blood loss in patients, and also mortality in rabbits.
In this rabbit model, PROGENIX® DBM Putty did not appear to function favorably as a stand-alone graft material. Histological sectioning of the stand-alone group showed no evidence of negative graft characteristics other that diminished bone-forming in comparison to the 3.0cc Autograft, extender, and enhancer groups. While we did not attempt to further characterize the diminished fusion activity of the stand-alone group, this may present an opportunity for further investigations with PROGENIX® DBM as a carrier for materials such as bone-marrow-aspirate or synthetic BMP's in this or other experimental models.
Our Faxitron-based radiographic fusion assessment and histologic analysis concurred with the manual palpation results. The addition of CT-based imaging in this study adds a novel assessment of fusion that is one of the options available for similar assessments in humans28. Although there is some controversy with regard to CT-based assessment of fusion in humans29–35;35, many of the options that are available for fusion assessment remain in the radiology realm. While the present study did not make attempts to fully characterize fusion rates based upon the CT-based imaging, this may be a relevant and timely assessment for future studies. Such assessments would need to be compared to other standards of assessment in this model (faxitron radiographs, manual palpation, and histological evaluation) for such a method to become further validated. Yet, this idea has been previously proposed as an acceptable adjunct to plain radiographic assessment in the rabbit model36.
The results of this rabbit study suggest that PROGENIX® DBM Putty is effective in producing a posterolateral fusion by radiographic and manual palpation criteria in an extender and enhancer mode. While animal models cannot be translated into clinically successful human applications, the results of this study suggest that further investigation into use of PROGENIX® DBM Putty as an autograft extender or enhancer in a human clinical setting may be appropriate.
Conclusions:
In this commonly used rabbit posterolateral fusion model, PROGENIX® DBM Putty in an autograft extender or enhancer mode produced manual palpation and radiographic fusion rates slightly better than autograft fusion (3cc) alone. When a lower volume of autograft was used, the PROGENIX® Putty was able to extend the autograft and improve fusion rates in comparison to the less than optimal autograft volume. These results were also slightly better than the full 3cc autograft volume, demonstrating enhancer capability. These findings indicate that PROGENIX® Putty was able to both extend (overcome inadequate autograft volume) and enhance (improve fusion rates over adequate volume of autograft) performance of autograft – as per the prior definitions of these terms20. This finding has important clinical implications in that autograft volume is often limited and harvest is associated with morbidity, additional surgical time and blood loss.
It is hypothesized that PROGENIX® Putty mixed with autograft has the ability to improve fusion performance by creating a homogeneous graft construct that provides a contiguous lattice between the osteogenic autograft particles. It appears to have the ability to act as both an osteoconductive and osteoinductive bone graft that works to improve the autograft construct. The material properties of this construct subjectively improved the handling characteristics in comparison to autograft alone, and objectively resisted migration intraoperatively and during the bone formation process.
PROGENIX® Putty when used alone or in combination with autograft induced de novobone formation and remodeled into host bone as evidenced by histologic and radiographic appearance. The rate of remodeling also was greater for the PROGENIX® Putty material than for the autograft, likely due to the mineral content (mineralized vs. demineralized bone).
Although the rabbit posterolateral model is well characterized and provides a challenging bone healing environment, results cannot be extrapolated to the human clinical environment. Further studies would be necessary to determine how the results observed in this study correlate to those that may be observed with similar use in humans.
Footnotes
Funding: Portions of this study were funded by a grant to the University of Iowa from Medtronic Sofamor Danek, Memphis, TN.
Device Status: PROGENIX® is FDA approved as a bone void filler for human use.
Disclosures: The authors report no other conflicts of interest – consultancy agreements, royalties, gifts received, intellectual property with regard to the products (PROGENIX®) or company (Medtronic) involved in this scientific investigation.
References
- 1.Arrington ED, Smith WJ, Chambers HG, et al. Complications of iliac crest bone graft harvesting. Clin. Orthop.Relat Res. 1996:300–9. doi: 10.1097/00003086-199608000-00037. [DOI] [PubMed] [Google Scholar]
- 2.Ebraheim NA, Elgafy H, Xu R. Bone-graft harvesting from iliac and fibular donor sites: techniques and complications. J.Am.Acad.Orthop.Surg. 2001;9:210–8. doi: 10.5435/00124635-200105000-00007. [DOI] [PubMed] [Google Scholar]
- 3.Hu R, Hearn T, Yang J. Bone graft harvest site as a determinant of iliac crest strength. Clin.Orthop.Relat Res. 1995:252–6. [PubMed] [Google Scholar]
- 4.Hu RW, Bohlman HH. Fracture at the iliac bone graft harvest site after fusion of the spine. Clin.Orthop. Relat Res. 1994:208–13. [PubMed] [Google Scholar]
- 5.Kahn B. Superior gluteal artery laceration, a complication of iliac bone graft surgery. Clin.Orthop.Relat Res. 1979:204–7. [PubMed] [Google Scholar]
- 6.Kurz LT, Garfin SR, Booth RE., Jr Harvesting autogenous iliac bone grafts. A review of complications and techniques. Spine. 1989;14:1324–31. doi: 10.1097/00007632-198912000-00009. [DOI] [PubMed] [Google Scholar]
- 7.Lim EV, Lavadia WT, Roberts JM. Superior gluteal artery injury during iliac bone grafting for spinal fusion. A case report and literature review. Spine. 1996;21:2376–8. doi: 10.1097/00007632-199610150-00015. [DOI] [PubMed] [Google Scholar]
- 8.Sasso RC, Williams JI, Dimasi N, et al. Postoperative drains at the donor sites of iliac-crest bone grafts. A prospective, randomized study of morbidity at the donor site in patients who had a traumatic injury of the spine. J.Bone Joint Surg.Am. 1998;80:631–5. doi: 10.2106/00004623-199805000-00003. [DOI] [PubMed] [Google Scholar]
- 9.Silber JS, Anderson DG, Daffner SD, et al. Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine. 2003;28(2):134–9. doi: 10.1097/00007632-200301150-00008. [DOI] [PubMed] [Google Scholar]
- 10.St John TA, Vaccaro AR, Sah AP, et al. Physical and monetary costs associated with autogenous bone graft harvesting. American Journal of Orthopedics (Chatham, Nj) 2003;32(1):18–23. [PubMed] [Google Scholar]
- 11.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. doi: 10.1302/0301-620X.71B4.2768321. [DOI] [PubMed] [Google Scholar]
- 12.Xu R, Ebraheim NA, Yeasting RA, et al. Anatomic considerations for posterior iliac bone harvesting. Spine. 1996;21:1017–20. doi: 10.1097/00007632-199605010-00004. [DOI] [PubMed] [Google Scholar]
- 13.Boden SD, Schimandle JH, Hutton WC. An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine. 1995:412–20. doi: 10.1097/00007632-199502001-00003. [DOI] [PubMed] [Google Scholar]
- 14.Boden SD, Schimandle JH, Hutton WC. Lumbar intertransverse-process spinal arthrodesis with use of a bovine bone-derived osteoinductive protein. A preliminary report. Journal of Bone & Joint Surgery - American Volume. 1995;77(9):1404–17. doi: 10.2106/00004623-199509000-00017. [DOI] [PubMed] [Google Scholar]
- 15.Boden SD, Schimandle JH, Hutton WC, et al. In vivo evaluation of a resorbable osteoinductive composite as a graft substitute for lumbar spinal fusion. Journal of Spinal Disorders. 1997;10(1):1–11. [PubMed] [Google Scholar]
- 16.Boden SD, Martin GJ, Jr, Morone M, et al. The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion. Spine. 1999;24(4):320–7. doi: 10.1097/00007632-199902150-00003. [DOI] [PubMed] [Google Scholar]
- 17.Grauer JN, Erulkar JS, Patel TC, et al. Biomechanical evaluation of the New Zealand white rabbit lumbar spine: a physiologic characterization. Eur. Spine. J. 2000;9:250–5. doi: 10.1007/s005860000141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Grauer JN, Vaccaro AR, Kato M, et al. Development of a New Zealand white rabbit model of spinal pseudarthrosis repair and evaluation of the potential role of OP-1 to overcome pseudarthrosis. Spine. 2004;29:1405–12. doi: 10.1097/01.brs.0000129028.25671.96. [DOI] [PubMed] [Google Scholar]
- 19.Grauer JN, Patel TC, Erulkar JS, et al. 2000 Young Investigator Research Award winner. Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion. Spine. 2001;26(2):127–33. doi: 10.1097/00007632-200101150-00004. [DOI] [PubMed] [Google Scholar]
- 20.Boden SD. Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute. Spine. 2002;27:S26–S31. doi: 10.1097/00007632-200208151-00007. [DOI] [PubMed] [Google Scholar]
- 21.Kraiwattanapong C, Boden SD, Louis-Ugbo J, et al. Comparison of Healos/bone marrow to INFUSE(rhBMP-2/ACS) with a collagen-ceramic sponge bulking agent as graft substitutes for lumbar spine fusion. Spine. 2005;30:1001–7. doi: 10.1097/01.brs.0000160997.91502.3b. [DOI] [PubMed] [Google Scholar]
- 22.Magit DP, Maak T, Trioano N, et al. Healos / recombinant human growth and differentiation factor-5 induces posterolateral lumbar fusion in a New Zealand white rabbit model. Spine. 2006;31:2180–8. doi: 10.1097/01.brs.0000232823.82106.0a. [DOI] [PubMed] [Google Scholar]
- 23.Bozic KJ, Glazer PA, Zurakowski D, et al. In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion. Spine. 1999;24(20):2127–33. doi: 10.1097/00007632-199910150-00012. [DOI] [PubMed] [Google Scholar]
- 24.Long J, Lewis S, Kuklo T, et al. The effect of cyclooxygenase-2 inhibitors on spinal fusion. Journal of Bone & Joint Surgery - American Volume. 2002;84A(10):1763–8. doi: 10.2106/00004623-200210000-00004. [DOI] [PubMed] [Google Scholar]
- 25.Liao SS, Guan K, Cui FZ, et al. Lumbar spinal fusion with a mineralized collagen matrix and rhBMP-2 in a rabbit model. Spine. 2003;28(17):1954–60. doi: 10.1097/01.BRS.0000083240.13332.F6. [DOI] [PubMed] [Google Scholar]
- 26.Lehman RA, Jr, Kuklo TR, Freedman BA, et al. The effect of alendronate sodium on spinal fusion: a rabbit model. Spine Journal: Official Journal of the North American Spine Society. 2004;4(1):36–43. doi: 10.1016/s1529-9430(03)00427-3. Feb. [DOI] [PubMed] [Google Scholar]
- 27.Tay BK, Le AX, Heilman M, et al. Use of a collagen-hydroxyapatite matrix in spinal fusion. A rabbit model. Spine. 1998;23(21):2276–81. doi: 10.1097/00007632-199811010-00005. [DOI] [PubMed] [Google Scholar]
- 28.Singh K, Smucker JD, Gill S, et al. Use of recombinant human bone morphogenetic protein-2 as an adjunct in posterolateral lumbar spine fusion: a prospective CT-scan analysis at one and two years. J.Spinal Disord.Tech. 2006;19:416–23. doi: 10.1097/00024720-200608000-00008. [DOI] [PubMed] [Google Scholar]
- 29.Chafetz N, Cann CE, Morris JM, et al. Pseudarthrosis following lumbar fusion: detection by direct coronal CT scanning. Radiology. 1987;162(3):803–5. doi: 10.1148/radiology.162.3.3809497. [DOI] [PubMed] [Google Scholar]
- 30.Cizek GR, Boyd LM. Imaging pitfalls of interbody spinal implants. Spine. 2000;25(20):2633–6. doi: 10.1097/00007632-200010150-00015. [DOI] [PubMed] [Google Scholar]
- 31.Epstein NE, Silvergleide RS. Documenting fusion following anterior cervical surgery: a comparison of roentgenogram versus two-dimensional computed tomographic findings. Journal of Spinal Disorders & Techniques. 2003;16(3):243–7. doi: 10.1097/00024720-200306000-00003. [DOI] [PubMed] [Google Scholar]
- 32.Herzog RJ, Marcotte PJ. Assessment of spinal fusion. Critical evaluation of imaging techniques. Spine. 1996;21(9):1114–8. doi: 10.1097/00007632-199605010-00027. [Review] [5 refs] [DOI] [PubMed] [Google Scholar]
- 33.Kuklo TR, Rosner MK, Polly DW., Jr Computerized tomography evaluation of a resorbable implant after transforaminal lumbar interbody fusion. Neurosurgical Focus. 2004;16(3):E10. doi: 10.3171/foc.2004.16.3.11. [DOI] [PubMed] [Google Scholar]
- 34.Lang P, Genant HK, Chafetz N, et al. Three-dimensional computed tomography and multiplanar reformations in the assessment of pseudarthrosis in posterior lumbar fusion patients. Spine. 1988;13(1):69–75. doi: 10.1097/00007632-198801000-00017. [DOI] [PubMed] [Google Scholar]
- 35.Spruit M, Meijers H, Obradov M, et al. CT density measurement of bone graft within an intervertebral lumbar cage: increase of hounsfield units as an indicator for increasing bone mineral content. Journal of Spinal Disorders & Techniques. 2004;17(3):232–5. doi: 10.1097/00024720-200406000-00011. [DOI] [PubMed] [Google Scholar]
- 36.Yee AJ, Bae HW, Friess D, et al. Accuracy and interobserver agreement for determinations of rabbit posterolateral spinal fusion. Spine. 2004;29(12):1308–13. doi: 10.1097/01.brs.0000127184.43765.61. [DOI] [PubMed] [Google Scholar]