Molecular Methods of Enhancing Lumbar Spine Fusion

Jason P. Sheehan, M.S., David F. Kallmes, M.D., Jonas M. Sheehan, B.A., John A. Jane, Jr., B.A., Allan H. Fergus, B.S., Charles G. diPierro, M.D., Nathan E. Simmons, M.D., David D. Makel, Ph.D., Gregory A. Helm, M.D.

Departments of Neurological Surgery (JPS, JMS, JAJ, AHF, CGdP, NES, GAH), Radiology (DFK), Biomedical Engineering (DDM), and Biophysics (JPS), University of Virginia, Charlottesville, Virginia

OBJECTIVE: An optimal method for spinal fusion would induce rapid growth of bone via an osteoconductive and osteoinductive implant. This study examines the spinal fusion enhancement potential of some osteoconductive and osteoinductive biomaterials.
METHODS: Four similar canines received unilateral posterolateral fusions on the left side at T13­L1 and L4­L5 and on the right side at L2­L3 and L6­L7. The experiments were grouped as follows: Group A, autogenous bone harvested from the iliac crest; Group B, autogenous bone and collagen; Group C, no implant; and Group D, autogenous bone, collagen, and recombinant human bone morphogenetic protein-2. Radiographic assessment, three-dimensional computed tomographic volumetric analysis, and biomechanical testing were performed at each level.
RESULTS: For Groups A and B, the fusions demonstrated moderate bone formation at 6 and 12 weeks postoperatively. Group D fusions exhibited earlier and more dramatic increases in volume and radiodensity and eventually were comparable in size to the vertebral bodies. Average fusion volumes computed from three-dimensional computed tomographic analysis were: Group A = 1.243 cc, Group B = 0.900 cc, Group C = 0.000 cc, and Group D = 6.668 cc (P = 0.003 compared to Group A). Group D exhibited flexion and extension biomechanical properties much greater than controls. The addition of recombinant human bone morphogenetic protein-2 consistently yielded the strongest fused segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over controls.
CONCLUSION: The most advantageous spinal fusion implant matrix consisted of recombinant human bone morphogenetic protein-2, autogenous bone, and collagen. Future investigators, however, need to examine the appropriate quantities of the individual components and clarify the efficacy of the matrix for the various types of spinal fusion approaches.
(Neurosurgery 39:548­554, 1996)

Key words: Bone morphogenetic protein, Osteoconduction, Osteoinduction, Spinal fusion

Spinal fusion plays a significant role in the treatment of conditions including spinal trauma, tumors, congenital abnormalities, and degenerative diseases (8, 16). Long-term stability in spinal fusion either with or without instrumentation can only be achieved by creating a solid bone arthrodesis. The most significant obstacles in all spinal fusions are poor bone deposition at the fusion site and pseudoarthroses. Moreover, poor bone material properties (e.g., trabecular thickness and mineralized volume and rate) at the fusion site are a particular problem with fusions without instrumentation (12). Autogenous bone grafts are typically used to create a solid bone fusion mass and remain the gold standard (19, 21). Unfortunately, it can be difficult to obtain adequate quantities of bone and the grafts are prone to resorption (10, 21). Moreover, harvesting bone from sites such as the iliac crest or ribs can be painful and increase morbidity (21, 22, 29, 34). Cryopreserved allograft bone has disadvantages of a lower fusion rate and a higher risk of infection compared to autogenous bone grafts (17, 19, 21, 29, 34).

An optimal method for spinal fusion would induce rapid growth of bone at the site via an osteoconductive and osteoinductive implant. One of the first successful attempts at induction of bone growth was achieved using demineralized bone (26). These implants, however, fused inconsistently, tended to be resorbed, and carried the risk of transmission of infectious agents. In another attempt to augment spinal fusion, calcium hydroxyapatite, tricalcium phosphate, and bioglass were implanted into canine spines (18). In those experiments, the calcium hydroxyapatite was the only biomaterial that was incorporated into surrounding trabecular bone; unfortunately, hydroxyapatite alone exhibits poor tensile strength (18) (Costantino PD, Loyola University Medical Center, personal communication, 1995).

More recently, osteogenic growth factors found in demineralized bone and termed bone morphogenetic proteins (BMPs) have been isolated (27). BMPs have been shown to induce transformation and differentiation of mesenchymal cells into osteoblasts (2, 28). Moreover, in situ hybridization studies have illustrated that BMP messenger RNAs are present at the appropriate times and locations during embryonic skeletal development (30). Mammalian serine/threonine kinase receptors (CFK-43A and BRK-1), which have high binding affinities for BMP-2 and -4 but low affinities for transforming growth factor-beta, are expressed in developing limb buds (13, 32). The role of BMPs in bone formation seems indisputable.

Through molecular cloning, nine BMPs have been identified (21). With the exception of BMP-1, BMPs are members of the transforming growth factor-beta superfamily of growth factors and are found in minute quantities in bone. To isolate 1 mg of BMP with current extraction and purification techniques, 1000 kg of bone would be needed (9). Using genetically modified cell lines, recombinant BMP can be produced in vitro in virtually unlimited quantities (31). Recombinant human BMP-2 (rhBMP-2) is free of infectious agents and contaminants that could potentially affect osteoinduction. Another advantage of rhBMP-2 is that the molecule is of human origin and thus does not elicit the same worry of rejection or partial response as xenogeneic agents.

Previous research has shown that the osteoinductive effect that occurs after administration of BMP-2 continues for approximately 6 months (24). In the absence of an appropriate carrier, hemorrhage and edema can act to dilute or wash out the growth factor from the intended location, but the best carrier for rhBMP-2 has yet to be determined. In this study, a potential osteoconductive carrier of bovine Type I collagen was used to bind and deliver the growth factor. Collagen has been shown to provide a framework onto which osteoblasts can freely migrate (6, 7, 23). The goal of this research was to examine radiologically and biomechanically whether the addition of collagen and rhBMP-2 would improve spinous process, lamina, and facet autogenous bone lumbar fusions.


Four adult female beagles of comparable size and age were used in this study. Unilateral, posterior lumbar fusions were attempted with various graft materials. The fusion technique adopted is that described by DiPierro et al. (8) and entails a spinous process, lamina, and facet fusion.

Animals in Group A received autogenous bone alone harvested from both iliac crests. Animals in Group B received fusion grafts of bovine Type I collagen gel and autogenous bone. Animals in Group C received no implant and served as the controls. Animals in Group D received fusion grafts consisting of Type I collagen gel, autogenous bone, and bone morphogenetic protein-2 (rhBMP-2). Each of four canines was fused at the following two vertebral levels: left side of T13­L1, right side of L2­L3, left side of L4­L5, and right side of L6­L7. The four graft materials were rotated through the different lumbar sites to minimize any effects that the level might have.

The animals were killed 12 weeks postoperatively with a phenobarbital/pentobarbital mixture. Specimens were delicately excised, cleaned of soft tissue, and subjected to gross examination and biomechanical flexion and extension testing.

Operative technique

The animals were anesthetized with 50% tiletamine/50% zolazepam (10 mg/kg) (Telazol; Fort Dodge Laboratories, Fort Dodge, IA), intubated, and placed under Halothane (Halocarbon Laboratories, River Edge, NJ) anesthesia. The lower back was shaved, prepared, and draped in sterile fashion; a midline incision was made from T12 to S1. The lumbodorsal fascia was incised at the appropriate levels and the paraspinous musculature was elevated from the spinous processes and laminae. At this point, decortication of laminae, facets, and spinous processes was performed with a high-speed drill at the following levels: left side of T13­L1; right side of L2­L3; left side of L4­L5; and right side of L6­L7. Hemostasis was achieved with bipolar cautery and Gelfoam (Upjohn, Kalamazoo, MI). The alternating implant scheme prevented migration of graft material between levels. Moreover, each canine had three different implants and a no implant control. Such an arrangement permitted the evaluation and minimization of bias caused by fusion site differences.

Next, incisions were made bilaterally to expose the iliac crests. Bone chips were removed using rongeurs, and the bone was washed and stored in sterile normal saline solution. The iliac crest incisions were then closed in three layers.

In Group A, 2.6 g of autogenous bone chips were added over the fusion level. In Group B, the fusion implant contained 2.6 g of bone chips and 1 g of bovine Type I collagen rehydrated into a cohesive paste material with 2 ml of 0.9 mol/L sterile saline (ReGen Biologics, Franklin Lakes, NJ) (14). Group C had no implants. The Group D implants consisted of 1 g of collagen, 2 ml of sterile saline, 2.6 g of bone chips, and 1.6 mg of rhBMP-2 (Genetics Institute, Cambridge, MA). The fascial layer was then closed in an interrupted fashion using 3­0 Nurolon sutures (Ethicon, Inc., Somerville, NJ). Subcutaneous tissue was closed in an interrupted fashion using 3­0 Vicryl sutures (Ethicon, Inc.), and the skin was closed with 3­0 Dermalon (American Cyanamid Co., Danbury, CT). The canines received postoperative analgesia as needed and postoperative antibiotics for 3 days.

Preparation of bovine Type I collagen

The Type I collagen (ReGen Biologics) was extracted from bovine Achilles tendon and purified by chemical treatments that included water, salt, base, and solvent extractions to eliminate noncollagenous components. Analysis of the collagen revealed that it included the following: 0.03% hexosamine, 13% hydroxyproline, 0.01% neutral sugars, and trace contamination by glycoproteins and glycosaminoglycans (14). The particle size of the dehydrated collagen was <450 mum (14). At pH = 7.4, the collagen molecules carry a net negative charge. Coulombic interactions between negatively charged fibers result in microscopic fibril repulsion and macroscopic swelling into a cohesive, paste-like matrix.

The collagen was tested for cytotoxicity, sterility, hemolysis, pyrogenicity, mutagenicity, and immunogenicity. Cytotoxicity, sterility, hemolysis, pyrogenicity were tested for in accordance with United States Pharmacopeia XXII (25). A modified Ames test was performed to assess mutagenicity (1). Using enzyme-linked immunosorbent assay, the humoral immune response was examined in a rabbit model. Finally, a mouse host was used to examine the immune response to the collagen. In all cases, the results of the safety studies were consistent with the safety requirements for implantable materials.

Computed tomography

Computed tomographic (CT) scans were obtained at 1, 6, and 12 weeks postoperatively. Canines were anesthestized with 50% tiletamine/50% zolazepam (10 mg/kg) and scanned in the supine position. Scanning was performed on a Picker PQ-2000 (software version 4.2; Picker International, Cleveland, OH). Axial images with a 2.0-mm collimation and 1.5-mm table increment were performed using a standard algorithm, with conditions of 130 kV, 150 mA, and 2-second scan time per slice. The field of view was set to 24 cm, with a display field of 12 cm.

Volumetric analysis was performed on a Voxel Q workstation (Picker International). A binary image was created by setting the window to zero (0) Hounsfield units. A level of 100 Hounsfield units was chosen, because preliminary data demonstrated that this level most accurately correlated with the volume of cortical bone. Volumetric data were generated based on slice thickness and number of pixels per slice with attenuation values greater than or equal to100 Hounsfield units. Regions of interest were manually created to include only posterior elements. The region of interest was further subdivided by drawing a coronal line bisecting the spinal canal. Using the 12-week postoperative scans, the cortices of intact posterior elements were easily distinguished from adjacent bone grafts. Computer-aided hand segmentation was performed to exclude the intact posterior elements and yield the volume of the new bone graft.

Biomechanical testing

The spines were excised, grossly cleaned of soft tissue, and rinsed in physiological saline solution. To attach to the vertebral bodies during biomechanical testing, the bodies were placed into a mold, and cerro metal was poured around them and allowed to cool. Cerro metal, an alloy of bismuth, tin, cadmium, and lead, melts at 70šC and was therefore ideal for specimen mounting. After removal from the mold, each entire spinal segment consisting of two vertebrae and the intervening intravertebral disc could be tested biomechanically. The vertebral bodies were fixed to an apparatus designed to measure the degree of flexion and extension displacement of the segment as a function of applied force. Angles of deflection were taken as a function of a 500-g load applied. Then, knowing the length of the spinal segment, the applied torques per degree of deflection in either flexion or extension were computed.


Gross examination

Immediately following removal, gross examination of the specimens demonstrated that some degree of fusion had occurred at all levels in Groups A, B, and D. No evidence of pseudoarthrosis was noted. Upon manual palpation of intact grafted spines, no motion was demonstrated and they were declared grossly fused. However, fusion masses from Group A (autogenous bone) and Group B (autogenous bone and collagen), both of which were without rhBMP-2, appeared more porous than those from Group D (with rhBMP-2). Groups A and B were also variable in size, indicating inconsistent bone formation, whereas the fusion thickness and surface characteristics of Group D were much more uniform and consistent. Gross examination of Group D specimens demonstrated that fusion masses were comparable in size to the vertebral bodies; this observation is consistent with the radiological findings.

Radiological assessment

The CT scans and the anteroposterior and lateral radiographs demonstrated that Group A (autogenous bone) and Group B (bone and collagen) had significant amounts of new bone formation at 6 and 12 weeks postoperatively. Group D (with rhBMP-2) fusions exhibited earlier and more dramatic volume and radiodensity increases with time as compared to Groups A and B; at 12 weeks postoperatively, the rhBMP-2 fusions were comparable in size to the vertebral bodies. No appreciable bone growth, resorption, or fusion was noted for Group C. Figure 1 illustrates these observations with axial images of all the different implant groups 12 weeks postoperatively. In addition, Figure 2, a longitudinal three-dimensional (3-D) CT reconstruction of the same canine again at 12 weeks postoperatively, permits further comparison of all of the implant materials.

Volumetric analyses of the fusion masses were performed using 3-D CT reconstructions. The results in Figure 3 are the fusion volumes at 12 weeks postoperatively. As expected, Group C (i.e., the control group) exhibited no change in bone volume. Group A fusion volume was 1.243 ± 0.124 cc (± standard error of the mean with a sample size of 4). With the addition of collagen to the bone chips, the fusion volume for Group B was 0.899 ± 0.325 cc, which constituted a 27.7% decrease from that of autogenous bone alone. For Group D, the fusion volume was significantly increased to 6.668 ± 1.139 cc, 536% more than autogenous bone alone. Statistically significant differences exist among Groups A, B, and D and the controls in Group C. Of more interest, statistically significant differences (P = 0.003 in both cases using an unpaired Student's t test) in fusion volume exist between Group D and either Group A or B.

FIGURE 1. Axial cuts of 3-D reconstructions of canine spinal segments 12 weeks postoperatively. All axial cuts shown are representative of those seen throughout the study. The decortication and subsequent bone fusion sites (except for the Group C controls) appear over the laminae on the right. A, Group A autogenous bone implant achieved a large, solid bone fusion. B, Group B autogenous bone and collagen implants attained a smaller and less solid bone fusion than in Group A. C, Group C (no implant controls) had no change in bone volume or radiodensity during the postoperative period. D, Group D, containing rhBMP-2, autogenous bone, and collagen, achieved a very solid and massive bone fusion. The rhBMP-2-based fusion is even larger than the vertebral body.

FIGURE 2. A longitudinal view of a 3-D reconstruction of a canine spine 12 weeks postoperatively. The implant containing rhBMP-2 (Group D) clearly contains more bone, followed in descending order of volume by the autogenous bone implant (Group A), the autogenous bone and collagen implant (Group B), and, last, the control with no implant (Group C).

FIGURE 3. Spinal fusion volumes at 12 weeks postoperatively. CT volumetric analysis of the 12-week postoperative scans demonstrated that Group D (collagen, bone, and rhBMP-2 [D]) implants resulted in the largest fusion volume and that it was statistically significant (P = 0.003) from the volumes of both Group A (autogenous bone [A]) and Group B (collagen and bone [B]) fusions. Group C (control [C]) had no change in volume during the 12-week period. SEM, standard error of the mean; CC, cubic centimeters.

Biomechanical analysis

Of the 16 samples tested, none was biomechanically unstable enough to fail under the applied loads up to 0.720 N € m torque (equivalent to a 500-g load applied to a lever arm of two vertebral bodies in length). However, there were substantial differences between some of the groups. The control group (i.e., Group C), which received only a simple decortication and no implant, demonstrated extension and flexion stiffness of 0.239 ± 0.048 and 0.132 ± 0.015 N € m/degree (± standard error of the mean with a sample size of 4), respectively. In Group A, the extension and flexion results of specimens fused with autogenous bone alone were 0.679 ± 0.246 and 0.666 ± 0.237 N € m/degree, respectively. With the addition of collagen, Group B extension and flexion stiffness decreased to 0.304 ± 0.140 and 0.417 ± 0.248 N € m/degree, respectively. Group D spines, which contained rhBMP-2, had markedly increased stiffness in extension and flexion of 1.496 ± 0.517 (P = 0.052; unpaired Student's t test relative to controls) and 1.475 ± 0.662 N € m/degree (P = 0.089; unpaired Student's t test relative to controls), respectively. Thus, Group D stiffness in both flexion and extension approached statistical significance as compared to the controls in Group C.

In Figure 4, spinal fusion with autogenous bone alone shows enhancement of biomechanical stability. The addition of collagen to the fusion matrix yields a slight biomechanical improvement over the controls. However, in both extension and flexion, collagen decreased the overall fusion biomechanical strength compared to autogenous bone. The addition of rhBMP-2 to the fusion implant consistently yielded the strongest fusion segments and, on average, enhanced extension stiffness by 626% and flexion stiffness by 1120% over that of the controls. Also, as is perhaps intuitive, high mathematical correlations existed between extension and flexion stiffness within each particular group. The average correlation coefficient (R2) for all four groups was 0.925. Therefore, a specimen that was strong in extension stiffness also was very likely to exhibit strength in flexion stiffness.

FIGURE 4. Biomechanical strength of the fusions in extension (solid bars) and flexion (hatched bars). The stiffness of the fusion specimens in extension and flexion demonstrated that spines from Group D (collagen, bone, and rhBMP-2 [D]) were the strongest. Group C (control [C]) had the weakest specimens and Groups A (autogenous bone [A]) and Group B (collagen and bone [B]) were intermediate in strength. Group A fusions on average were stronger than those in Group B. SEM, standard error of the mean; deg, degree.


The radiographs and 3-D CT volumetric analysis clearly demonstrate substantial bone formation (P = 0.003) at the sites containing rhBMP-2 implant material relative to autogenous bone or autogenous bone and collagen fusions. At sites containing collagen and/or autogenous bone, the bone formation was variable and clearly diminished in quantity when compared with the rhBMP-2 containing sites. No significant bone formation or resorption was noted in the controls that lacked implants.

Biomechanical testing of the explants showed dramatic strength of the rhBMP-2 fusion sites over the controls. Moreover, the consistent biomechanical superiority of the rhBMP-2 implants, regardless of the spinal level, is indicative of a more uniform bone formation process compared to fusions without rhBMP-2. The stiffer fusion results with the autogenous bone (Group A) as compared to the autogenous bone and collagen (Group B) may be caused by a lower density of the fusion mass in the presence of collagen because collagen occupied significant volume in the implant. Furthermore, collagen alone has been shown to delay bone fusion (15).

When the 3-D CT volumetric analysis and the biomechanical testing results were compared, the statistical correlation coefficient (R2) between the fusion volume and the extension stiffness of a specimen was 0.974; the correlation coefficient between the fusion volume and the flexion stiffness of a specimen was 0.976. Thus, a strong correlation exists between the results of the 3-D CT volumetric analysis and the biomechanical testing. In other words, specimens that had larger fusion volumes also were more biomechanically stable. This result may seem obvious, but its significance is substantial. Providing that a solid fusion without pseudoarthrosis has been achieved, future researchers, particularly those conducting human investigations, may gain insight into the flexion and extension strength of a spinal fusion by measuring its fusion volume radiologically.

Several recent animal studies have demonstrated the usefulness of BMPs in the healing of skeletal defects. For instance, Yasko et al. (33) demonstrated that rhBMP-2 stimulated bone formation in a dose-related fashion in rats with 5-mm segmental defects in the femur. Yasko's work was extended by Gerhart et al. (9), who demonstrated that 2-cm femoral defects could be consistently healed with rhBMP-2. In mandibular defects, Toriumi et al. (24) demonstrated that rhBMP-2 effectively healed 3-cm spans. Using a rabbit intertransverse process fusion model, Schimandle et al. (21) showed that rhBMP-2 increased both the strength and stiffness of autograft fusions. Another bone-inducing protein called rhOP-1 has proven effective in healing segmental osteoperiosteal defects in rabbits, dogs, and monkeys (4). This protein also seems to be of potential value in posterior spinal stabilization without the use of autograft (5). The present study has demonstrated that the application of an osteoinductive rhBMP-2, osteoconductive Type I collagen, and autogenous bone matrix increases the volume and biomechanical stability of lumbar spinous process, laminar, and facet fusions.

One limitation of this spinal fusion matrix was the fluidity of the collagen carrier in the implant compartment. Care must be exercised to contain the collagen carrier at the desired fusion site. This fluidity could limit the usefulness of the biomaterial for applications such as cranioplasty. Nevertheless, the fluid quality of collagen is also a beneficial intraoperative property. It can be applied surgically with a cannula or syringe, particularly where the bone defects are irregular or inaccessible by normal surgical means. The collagen carrier and rhBMP-2 implant material could even be administered during an endoscopic procedure. It is also the fluid state of collagen that enables it to establish good osteoconductive contact with the graft bone chips as well as the host bone.

Recent studies at other institutions with hydroxyapatite, which can be injected in a fluid state but hardens to the strength of bone at physiological temperatures within 10 minutes after implantation, have yielded some encouraging results (3, 11). The hydroxyapatite material seems to be an equally good carrier of bone morphogenetic protein with the advantage of easy and rapid containment both of the growth factor and the carrier at the desired site (20). Vascularization of the hydroxyapatite also has been observed within a reasonable timetable (Costantino PD, Loyola University Medical Center, personal communication, 1995). Hydroxyapatite seems to be useful for long bone and cranial defects, but its use in spinal fusion has not been adequately explored.

The ability of rhBMP-2 to enhance bone volume and biomechanical strength is clear, and the potential application of rhBMP-2 and collagen in addition to autogenous bone for spinal fusion looks promising. Moreover, the search for the best in vivo osteoconductive carrier for bone morphogenetic proteins continues with a number of possible candidates (e.g., fibrillar collagen, a collagen sponge, demineralized bone, polymethylmethacrylate, and hydroxyapatite preparations) and the outlook is hopeful. Future research must indicate the best carrier, optimize the appropriate quantities of the individual components, and better clarify the efficacy of the matrix for this and other spinal fusion techniques.


The authors thank Genetics Institute (Cambridge, MA) and ReGen Biologics (Franklin Lakes, NJ) for supplying components of the fusion biomaterials. In addition, we thank Dr. George Gillies of the University of Virginia Department of Biomedical Engineering (Charlottesville, VA) for assistance with the biomechanical testing. The authors have no personal or financial interest in any medical products used throughout this research.

Received, November 9, 1995.
Accepted, March 27, 1996.
Reprint requests: Jason P. Sheehan, M.S., Department of Neurological Surgery, Box 212, University of Virginia Health Sciences Center, Charlottesville, VA 22908.


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In this small study, the authors have demonstrated the benefit of recombinant human bone morphogenetic protein-2 (rhBMP-2) in bone formation. Interestingly, Group B (treated with autogenous bone and collagen) attained less bone fusion and was weaker biomechanically than Group A (treated with autogenous bone only). Is collagen detrimental to a strong fusion? Can a better carrier be found? On the other hand, bone formation in Group D, in which rhBMP-2 was added to the autogenous bone and collagen, was impressive. Consequently, several questions remain. How much rhBMP-2 is appropriate to use? Does instrumentation play a role in conjunction with rhBMP-2? Can a better carrier than collagen be found? Because the osteoinductive effect of rhBMP-2 continues for 6 months, will the eventual fusion mass become too bulky or too stiff?

In conclusion, the authors have documented the benefit of rhBMP-2 in fusion constructs in canines. Hopefully, further work from their laboratory and others will duplicate these results, answer the above questions, and eventually explain the definitive role of rhBMP-2 in a clinical setting.

Volker K.H. Sonntag
Phoenix, Arizona

Sheehan et al. have performed an interesting and valuable study of methods to perform spinal fusion and primarily to study the effectiveness of using recombinant bone morphogenetic protein (BMP). As expected, the BMP had a beneficial effect on enhancing the fusion and stiffness of the bone graft site.

It will be interesting to see what happens with the use of BMP when it is added without the presence of bone or when it is used with a combination of allograft and/or calcium apatite. If the recombinant BMP can enhance a fusion with any of those substances, less morbidity will occur with spinal fusions.

We are all awaiting the results of clinical trials of BMP. I hope they will be carried out soon and that they will be effective so that fusion surgery can be enhanced.

Stewart B. Dunsker
Cincinnati, Ohio

Biological enhancement of spinal fusion has become a promising area of clinically relevant spinal research. Little doubt exists that such techniques will have widespread clinical applicability in the near future. There are many potential benefits of these methods, including reduced pseudoarthrosis rates, biomechanically stronger fusion bone, and reduced donor site morbidity from diminished reliance on spinal implants. There is also significant potential for application of these methods with concurrent development of minimally invasive spinal surgery techniques. I look forward to further development of these promising methods of spinal stabilization.

Paul C. McCormick
New York, New York

Sheehan et al. have eloquently presented their laboratory experience with rhBMP-2 as an enhancer of lumbar spine fusion. They have statistically demonstrated that the addition of rhBMP-2 volumetrically increases bone growth in spinal fusion, compared to autograft controls. Although an increase in bone volume was observed with the addition of rhBMP-2 to autograft spinal fusion, a statistically significant increase in biomechanical strength was not shown, even when compared to "spine fusions" without graft. The authors stated that a statistically significant strength difference "was approached" between the no graft and autograft plus rhBMP-2 groups. Significance may have been achieved with an increase in the number of animals studied. An increased number of laboratory subjects might also provide additional information regarding the clinically relevant differences between autograft only and autograft plus rhBMP. This is clinically more relevant than comparisons between no graft and graft plus rhBMP.

An increased availability of BMP for laboratory research will increase the statistical power of future investigations by allowing larger studies to be performed. Other variables (such as dosage, efficacy of "carriers," and toxicity and complications) may also be addressed.

Sheehan et al. have clearly demonstrated the potential for BMP application to spinal surgery. They have also established foundation for future research. We, as well as many others, are eagerly anticipating the results of ongoing and future research in this exciting area of medicine. These results almost certainly will alter the manner in which we manage pathological diseases of the spine.

Michael A. Morone
Scott Boden

Orthopedic surgeon
Atlanta, Georgia

Edward C. Benzel
Albuquerque, New Mexico

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