In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion.

STUDY DESIGN: An animal model of posterolateral intertransverse process lumbar spinal fusion using autologous bone, coralline hydroxyapatite, and/or direct current electrical stimulation. OBJECTIVES: To evaluate the effect of an osteoconductive bone graft substitute and direct-current electrical stimulation on the rate of pseudarthrosis in a rabbit spinal fusion model. SUMMARY OF BACKGROUND DATA: Conventional techniques for the surgical treatment of degenerative conditions in the lumbar spine have a substantial failure rate and associated morbidity. Bone graft substitutes and electrical stimulation are alternative techniques to enhance fusion rates and limit the morbidity associated with posterolateral intertransverse process fusion using autologous iliac crest bone graft. METHODS: Fifty-three adult female New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were assigned to one of four groups using either autologous bone (Group I), coralline hydroxyapatite with autologous bone marrow aspirate (Group II), coralline hydroxyapatite with a 40-microA implantable direct current electrical stimulator and bone marrow aspirate (Group III), or coralline hydroxyapatite with a 100-microA implantable direct current electrical stimulator and bone marrow aspirate (Group IV). Animals were killed at 8 weeks, and fused motion segments were subjected to manual palpation, mechanical testing, and radiographic and histologic analysis to assess the fusion mass. RESULTS: Successful fusion was achieved in 57% (8/14) of animals in Group I, 25% (3/12) in Group II, 50% (6/12) in Group III, and 87% (13/15) in Group IV. Mean stiffness and ultimate load to failure were significantly higher in Group IV than in all other groups (P < 0.05). Histologic analysis demonstrated a qualitative increase in fusion mass in Group IV versus all other groups. CONCLUSIONS: Direct-current electrical stimulation increased fusion rates in a dose-dependent manner in a rabbit spinal fusion model. Coralline hydroxyapatite is an osteoconductive bone graft substitute, and thus requires an osteoinductive stimulus to ensure reliable fusion rates. Furthermore, coralline hydroxyapatite and direct current electrical stimulation can be used together to increase fusion rates in a rabbit spinal fusion model while avoiding the morbidity associated with harvesting iliac crest bone.     

New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis

STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To determine the efficacy of two new formulations of demineralized bone matrix. SUMMARY OF BACKGROUND DATA: The flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix has been shown to have osteoinductive properties in various models and currently is used clinically as bone graft material in posterolateral lumbar spine arthrodesis. Two new formulations of Grafton, one made of flexible sheets (Flex) and the other made in a malleable consistency (Putty), have improved handling characteristics compared with the gel form. METHODS: In this study, 108 New Zealand white rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone (control), one of the new forms of demineralized bone matrix (DBM; made from rabbit bone) alone or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks after surgery. The lumbar spines were excised, and fusion success or failure was determined by manual palpation and radiography. Specimens also were processed for undecalcified histologic analysis. RESULTS: Manual palpation of the harvested lumbar spines revealed that the fusion rates of the Flex-DBM/Auto group (9/9, 100%) and Putty-DBM/Auto group (10/10, 100%) were superior (P < 0.01) to those of the Auto/control group (3/9, 33%). As a stand-alone graft substitute, Flex-DBM performed superiorly with a fusion rate of 11/11 (100%) compared with that of Putty-DBM (10/12, 83%) and Gel-DBM (7/12, 58%). The devitalized version of Flex-DBM had a fusion rate of 4/11 (36%), which was comparable with the devitalized Putty-DBM rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized Gel-DBM rate of 0/12 (0%). More mature fusions with greater amounts of trabecular bone were present radiographically and histologically in rabbits that received all forms of demineralized bone matrix than in those in which autograft was used. CONCLUSIONS: The new flexible sheet and malleable putty forms of demineralized bone matrix were effective as graft extender and graft enhancer in a model of posterolateral lumbar spine fusion. These newer formulations of Grafton appear to have a greater capacity to form bone than the gel form or autogenous bone graft alone in this model.     

Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenetic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate.

STUDY DESIGN: A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate recombinant human bone morphogenetic protein 2 (rhBMP-2) in a hydroxyapatite-tricalcium phosphate (HA-TCP) carrier as a complete bone graft substitute. OBJECTIVES: To assess the ability of a ceramic material to serve as a carrier for various doses of rhBMP-2 as a bone graft substitute in a primate model of posterolateral intertransverse process spinal fusion after laminectomy. SUMMARY OF BACKGROUND DATA: The reported non-union rates for posterolateral lumbar spine fusion with autogenous iliac crest bone range from 5-35%. Recombinant human bone morphogenetic protein 2 has shown potential to serve as a bone graft substitute for posterolateral intertransverse process spine fusion. Although a resorbable collagen sponge was a suitable carrier in rabbits and dogs, it was too compressible for the paraspinal muscles in rhesus monkeys. This failure of the collagen carrier has prompted evaluation of the feasibility of an alternative carrier material and the required dose of rhBMP-2. METHODS: Twenty-one adult rhesus monkeys underwent a laminectomy at L4-L5 followed by bilateral intertransverse process arthrodesis via the same midline incision (n = 16) or a minimally invasive video-assisted posterolateral approach (n = 5). Bone graft implants on each side consisted of either 5 cm3 of autogenous iliac crest bone or 60:40 HA-TCP blocks (1.2 x 0.5 x 3.7 cm) loaded with a solution containing 0, 6, 9, or 12 mg of rhBMP-2 per side. The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, and histology were used to assess fusion and to detect any bony growth into the laminectomy defect. RESULTS: Fusion was not achieved in any of the monkeys treated with autogenous iliac crest bone graft. Both of the monkeys treated with the HA-TCP blocks with 0 mg rhBMP-2 achieved fusion. All 15 monkeys treated with the HA-TCP blocks and either of the three doses of rhBMP-2 achieved solid fusion. Two animals had extension of the fusion on one side because of malpositioned ceramic block. The results in animals fused via the minimally invasive video-assisted technique were the same as inthose fused with the open technique. Histologic analysis showed some ingrowth of bone into the ends but not-through the ceramic block in the absence of rhBMP-2. When the ceramic blocks were loaded with rhBMP-2 there was a dose-dependent increase in the amount and quality of bone throughout the ceramic carrier based on qualitative assessment. No significant bone encroachment on the exposed thecal sac through the laminectomy defect was observed in any of the monkeys. CONCLUSION: Hydroxyapatite-tricalcium phosphate proved to be a suitable carrier for rhBMP-2 in the posterolateral spine fusion model in rhesus monkeys. Even in the presence of a laminectomy defect, there was no evidence of bone induction outside the confines of the ceramic carrier.     

The efficacy of direct current stimulation for lumbar intertransverse process fusions in an animal model

STUDY DESIGN: Posterolateral lumbar intertransverse process fusion using a rabbit model with autologous bone graft and direct current stimulation was compared with fusion achieved by using autologous bone graft alone. OBJECTIVES: To determine the efficacy of direct current electrical stimulation for the posterolateral lumbar intertransverse process fusion technique by using a 20-microA current and the more recently developed 60-microA current delivered by an implantable direct current stimulator. SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated a positive effect of direct current electrical stimulation on posterior spinal fusion techniques. However, until recently, the environment of an intertransverse fusion was not well simulated. The current research examined the posterolateral lumbar intertransverse process fusion technique with direct current electrical stimulation using a rabbit model. This appears to parallel human fusion techniques more closely and allows for lower cost and technical ease. METHODS: In this study, 44 adult New Zealand white rabbits underwent an L5-L6 intertransverse process fusion. All the fusions used an autologous bone graft obtained from bilateral posterior iliac crests. A device was implanted in all the rabbits subcutaneously, and they were divided randomly into three groups: a sham or nonfunctioning group, a 20-microA low-current stimulator group, and a 60-microA higher-current stimulator group. Spinal fusion was evaluated radiographically, histologically, and manually as well as by biomechanical testing 5 weeks after surgery. RESULTS: Radiographic grades, manual palpation, biomechanical strength, and stiffness showed an increasing trend from sham or inactive stimulator groups to low-current and then to high-current stimulator groups. Histologic analysis revealed that the higher-current stimulator showed that, statistically, the healing response of the host tissue to the autograft had increased significantly, as compared with the sham. CONCLUSIONS: Direct current electrical stimulation is efficacious in improving both the healing rate and strength in this posterolateral lumbar fusion model. In addition, it appears that this effect is enhanced by increasing the stimulation current from 20 microA to 60 microA.     

Endoscopic instrumented posterolateral lumbar fusion with Healos and recombinant human growth/differentiation factor-5

OBJECTIVE: The goal of this study was to use a minimally invasive endoscopic surgical technique in a sheep model to evaluate the efficacy of an osteoinductive growth factor, recombinant human growth/differentiation factor-5 (also designated MP52), and an osteoconductive matrix formulation (Healos; DePuy AcroMed, Inc., Mountain View, CA) for inducing and facilitating bone formation. METHODS: Twelve mature sheep underwent bilateral posterolateral lumbar fusion and pedicle screw fixation via a posterior endoscopic approach. Each sheep received two different types of graft material, autogenous iliac crest bone, or a bone graft substitute (MP52 with Healos), inserted into the right and left sides of the spine in an alternating fashion. Groups of four sheep were killed at 2, 4, and 6 months postoperatively for manual, radiographic, and histological evaluation. RESULTS: No neurological impairments, infections, or other complications were observed. After 2 months, partial fusion on both sides was observed, but radiographic evaluation showed greater bone growth on the side that received the bone graft substitute. Solid posterolateral fusion was observed in both autograft and bone graft substitute sites at 4 and 6 months, and autograft and Healos MP52 fusion sites were essentially the same at histological examination. There was no abnormal overgrowth of new bone from either of these two materials. CONCLUSION: Endoscopic posterolateral lumbar arthrodesis and instrumentation is feasible, safe, and effective in a sheep model. Healos is a useful bonding agent that mimics natural bone in posterolateral intertransverse fusion sites. Combined with MP52, it produced fusion comparable to that of autogenous bone graft. Minimally invasive techniques and bone graft substitutes could eliminate morbidity and increase the likelihood of successful fusion.     

Osteogenic protein-1 overcomes the inhibitory effect of nicotine on posterolateral lumbar fusion

STUDY DESIGN: An established rabbit posterolateral lumbar fusion model was used to evaluate the ability of osteogenic protein-1 to overcome the inhibitory effect of nicotine. OBJECTIVE: To determine whether osteogenic protein-1 should be considered as a bone graft alternative for the patient who smokes. SUMMARY OF BACKGROUND DATA: Smoking interferes with the success of posterolateral lumbar fusion. This inhibitory effect has been attributed to nicotine and confirmed in a New Zealand white rabbit model. Osteoinductive protein-1 has been shown to induce posterolateral spine fusion reliably in the rabbit model. The effectiveness with which osteogenic protein-1 induces fusion in the presence of nicotine has not been studied previously. METHODS: Single-level posterolateral intertransverse process fusions were performed at L5-L6 in 18 New Zealand white rabbits. Either autograft or osteogenic protein-1 was used as grafting material. Nicotine was administered via subcutaneous mini-osmotic pumps. The animals were killed 5 weeks after surgery, and the resulting fusion masses were studied. RESULTS: Three rabbits (17%) were excluded because of complications. By manual palpation, two of the eight nicotine-exposed autograft rabbits (25%) and all of the nicotine-exposed osteogenic protein-1 rabbits (100%) were found to be fused. These results correlated well with those obtained from biomechanical testing. Histologically, the fusion zones of the nicotine-exposed autograft rabbits were distinctly less mature than the fusion masses of the nicotine-exposed osteogenic protein-1 rabbits. CONCLUSION: Osteoinductive protein-1 was able to overcome the inhibitory effects of nicotine in a rabbit posterolateral spine fusion model, and to induce bony fusion reliably at 5 weeks.     

The effect of osteogenic protein-1 in instrumented and noninstrumented posterolateral fusion in rabbits.

BACKGROUND CONTEXT: The use of rigid instrumentation combined with bone graft makes intuitive sense given the requirements for vascular ingrowth, bone formation and a stable environment for the cellular events of healing to develop. However, with the advances of potent osteoinductive growth factors, the role of internal fixation may come into question. Whether bone morphogenic proteins (BMPs) would benefit from a more "stable" spinal segment for bone production and modeling remains unknown. In addition, it is unknown whether BMP and rigid fixation may have an additive effect on fusion healing. PURPOSE: This study is proposed to test the hypothesis that rigid fixation in the lumbar spine would be advantageous to achieve fusion for autogenous bone grafting, but fusion would occur regardless of fixation with the use of osteogenic protein (OP)-1. STUDY DESIGN/SETTING: A histologic and radiographic analysis of BMP in a rabbit lumbar fusion model. METHODS: Thirty-two rabbits were randomized into four groups: 1) control animals: in situ posterolateral L5-L6 arthrodesis using autogenous iliac crest bone graft; 2) fixation group: posterolateral arthrodesis L5-L6 with autogenous bone graft and interspinous fixation; 3) OP-1 group: in situ posterolateral L5-L6 arthrodesis using OP-1 and 4) combined OP-1 and fixation group. Radiographic fusion analysis was performed with computed tomography scans at 3 and 12 weeks after surgery. Decalcified histology was performed to assess tissue morphology and cellularity. RESULTS: Minimal evidence of fusion was noted at 3 weeks with autograft or OP-1. By 12 weeks, all OP-1-treated animals had solid fusion, whereas no fusion was noted in autograft animals. The addition of fixation slightly increased radiographic fusion at 3 weeks in autograft and OP-1 groups but did not affect OP-1 animals at 12 weeks where all were fused. Decalcified histologic results confirmed the proliferative bone formation noted with OP-1 and the variable cellular response with autograft. CONCLUSIONS: The results of the present study suggest that the osteoinductive effect of OP-1 may be only minimally enhanced early in the bone healing process but does not appear to be affected in the long term by spinal fixation in the rabbit intertransverse fusion model. Fixation appeared to enhance early fusion in the autograft group.     

Flexibility analysis of posterolateral fusions in a New Zealand white rabbit model.

STUDY DESIGN: Biomechanics of posterolateral spinal fusion were studied in an in vivo rabbit model. OBJECTIVES: To determine the extent of stabilization produced by posterolateral lumbar fusion and to test the hypothesis that motions are not completely eliminated after successful fusion. SUMMARY OF BACKGROUND DATA: Previous human cadaveric studies, clinical studies, and animal studies have attempted to characterize the biomechanics of posterolateral fusion. Such studies have been limited by either methods of fusion modeling or methods of stability testing. No previous study has examined biologic fusion with a physiologic biomechanical testing technique. METHODS: Ten adult New Zealand white rabbits underwent L5-L6 intertransverse process fusion using autogenous iliac crest bone graft. Rabbits were killed 5 weeks after surgery. Only one time point was studied. This time point was chosen because previous pull-apart studies have shown plateauing of rabbit fusion mass strength and stiffness around this time. Spines were then harvested and evaluated with manual palpation and an established flexibility testing protocol. Resulting data were compared with previously acquired, nonoperative spine flexibility data. RESULTS: Two animals were excluded because of complications. Of those that were fused (n = 5), biomechanical testing revealed significant decreases in flexion (81%), extension (61%), and right and left lateral bending (67% and 83%, respectively) (P < 0.01). CONCLUSIONS: These findings define the amount of motion reduction that can be expected with posterolateral fusions in the rabbit model at 5 weeks. These results suggest that motion was significantly decreased but was not eliminated.     

The use of simvastatin in rabbit posterolateral lumbar intertransverse process spine fusion.

BACKGROUND CONTEXT: There has been recent enthusiasm regarding the potential positive effects of statins on bone. Statins vary in their ability to influence bone activity. Simvastatin has been shown in experimental models to stimulate bone acting growth factors and enhance bone formation. PURPOSE: The potential efficacy of Simvastatin in enhancing spinal fusion was evaluated in a rabbit posterolateral intertransverse process fusion model. STUDY DESIGN/SETTING: Posterior lumbar intertransverse process spinal fusion performed on New Zealand White rabbits. PATIENT/STUDY SAMPLE: 44 New Zealand White rabbits. OUTCOME MEASURES: Spinal fusion as determined by manual palpation testing and fine detail radiography. Bone fusion mass volume and density as determined by CT scan imaging. METHODS: Forty-four New Zealand White rabbits underwent posterolateral intertransverse process spine fusion using autogenous iliac crest bone graft. Simvastatin was administered orally in 20 animals and the serum lipid profile quantified in test and control animals. The animals were euthanized 9 weeks following index surgery and the lumbar spine was harvested. Spinal fusion was determined by manual palpation testing and fine detail radiography. The volume and density of the bone fusion mass was quantified by computed tomography. RESULTS: Drug treatment for 9 weeks caused a reduction in serum lipid biochemical markers when compared with controls. The spinal fusion rate, as judged by manual palpation testing (13.0% control group, 16.6% Simvastatin group) and fine detail radiography, was not significantly different comparing treatment with control animals. Accordant with the assessment of spinal fusion, there was no statistically significant effect on the volume of the fusion mass (1,224.7+/-98.7 mm(3) in the control group and 1,075.9+/-66.3 mm(3) in the Simvastatin group), the density of bone in the lumbar spine or that in the formed fusion mass. CONCLUSIONS: Systemic use of Simvastatin caused a reduction in lipid biochemical parameters in treated animals. Successful spinal fusion as judged by manual palpation testing and fine detail radiography was not significantly different in treated versus untreated animals. The bone volume density of the formed fusion mass was not significantly different in treated versus untreated animals. There did not appear to be a significant advantage or disadvantage to the use of Simvastatin rabbit posterolateral spinal fusion. The potential positive effects of statins on bone require further study.     

Stopping nicotine exposure before surgery. The effect on spinal fusion in a rabbit model

STUDY DESIGN: A double-blind, prospective, randomized study using a validated rabbit model of intertransverse process fusion. OBJECTIVES: To determine the effect of stopping prolonged nicotine exposure on autogenous bone graft incorporation in a rabbit lumbar spinal fusion model. SUMMARY OF BACKGROUND DATA: There is a growing body of evidence that systemic nicotine impairs healing of spinal fusions and fractures. However, it remains to be determined whether, if nicotine increases the nonunion rate of spinal fusion surgery, stopping nicotine exposure before surgery will negate this inhibitory effect. METHODS: Forty-seven rabbits were divided into two experimental groups and one control group. The two experimental groups were exposed to systemic nicotine for 8 weeks. Nicotine exposure was stopped in one group 1 week before surgery; nicotine exposure was continued in the other group throughout the study. All rabbits underwent an L5-L6 intertransverse process fusion with autogenous iliac crest bone graft. All rabbits were killed 35 days after surgery. Forty rabbits completed the study and underwent radiographic, biomechanical, and histologic testing. RESULTS: Fusion, as determined by a blinded examiner palpating the spine, occurred in 7 of 13 control rabbits, 4 of 13 rabbits that "quit" nicotine, and none of the 14 rabbits exposed to continuous nicotine. There was a statistically significant difference between the control and continuous nicotine (P = 0.0015) and between the discontinued nicotine and continuous nicotine groups (P = 0.025). Biomechanical testing showed no significant differences between groups (P = 0.11). A blinded musculoskeletal pathologist was unable to detect a difference between groups based on histologic analysis. CONCLUSIONS: Chronic nicotine exposure was shown to decrease spinal fusion rates. Discontinuing nicotine before surgery improved fusion rates.     

Autograft containment in posterolateral spine fusion.

BACKGROUND CONTEXT: Pseudoarthrosis rates in lumbar intertransverse fusion remain high. Compression and displacement of the developing fusion mass by the paraspinal musculature may be a contributory factor. Biocontainment devices have been clinically used in the skull and mandible to guide bone regeneration. The role of a mechanical device in containing graft material in the developing posterolateral lumbar spine fusion is unclear. PURPOSE: To determine the benefits of using a bioabsorbable graft-containment device for lumbar intertransverse fusion, and to evaluate the biocompatibility of this implant by histological analysis of the host tissue reaction. STUDY DESIGN: A rabbit intertransverse spine fusion model was used to evaluate a bioabsorbable graft-containment implant. Study and control groups were compared with regard to the rate, volume, and quality of fusion, as well as host tissue reaction to the graft and implant. METHODS: Fourteen adult male New Zealand White rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L3-L4. The control group (n=7) received autograft alone, and the study group received autografts placed in open meshed hemicylinders fashioned from LactoSorb sheets (LactoSorb; Biomet Orthopedics Inc., Warsaw, IN). Spines were harvested at 6 weeks and imaged. Radiographs and computed tomography (CT) images were used to calculate the rate, area, and volume of fusion mass. Sections were fixed and stained with hematoxylin-eosin and Mallory trichrome for histological analysis of fusion and host tissue response. The Mann-Whitney nonparametric statistical test was used for the radiographic and CT qualitative assessments. The CT volume quantitation was analyzed using the Student t test. A p value of <.05 was used to assign statistical significance. RESULTS: The fusion rates on radiographs and CT imaging did not show a significant difference (p>.05) between the biocontainment and control groups. The volume of fusion revealed a significant increase with biocontainment (mean+/-standard error; total left+right fusion sides=2.88+/-0.30 cc) compared with controls (2.12+/-0.15 cc) (p<.05). Histology revealed no difference in the maturity or the quality of the fusion mass between the two groups. Inflammatory response around the developing fusion mass and muscle necrosis were slightly increased in the study group. The LactoSorb biocontainment material led to variable inflammatory reaction, with some areas showing little or no response and other showing an inflammatory response with fibrous connective tissue, lymphocyte infiltration, and focal foreign body giant cell reaction. CONCLUSIONS: The incidence of fusion was similar with or without a containment device for onlay bone graft. A significant increase in the volume of the fusion suggests that a biocontainment device does play a role in protecting the developing fusion mass from the mechanical effects of the paraspinal musculature. The clinical use of this device cannot be justified at this time, and further studies will determine whether this increase in fusion volume will translate into a better incidence and volume of fusion in primate and human models.     

骨髓干细胞复合纳米骨用于脊柱融合的研究

目的 探讨骨髓间充质干细胞(BMSCs)复合纳米羟基磷灰石/胶原(nHAC)用于脊柱融合的可行性.方法 将20只新西兰大白兔根据双侧L5～L6横突间植入物不同分为复合材料组和自体髂骨组,每组10只.术后4周每组取材2只,术后8周取材剩余兔,行X线、大体观察、手触检测和组织学观察,评估腰椎融合情况.结果术后8周复合材料组和自体髂骨组融合率分别为75.0%(6/8)和87.5%(7/8),两组融合率差异无统计学意义(P>0.05).结论 BMSCs复合nHAC是一种较好的植骨替代材料,用于脊柱融合可获得与自体骨移植近似地融合效果.     

Efficacy of silicated calcium phosphate graft in posterolateral lumbar fusion in sheep.

BACKGROUND CONTEXT: Conditions requiring posterior lumbar spinal fusion remain a clinical challenge. Achieving arthrodesis using autogenous bone graft is inconsistent when rigid internal fixation such as transpedicular instrumentation is applied. Synthetic materials, particularly calcium phosphate-based ceramics, have shown promise for spine fusion applications, especially when combined with autograft. Silicate substitution has been shown to enhance the bioactivity of calcium phosphates and may obviate the need for autologous supplementation. PURPOSE: Determine efficacy of silicated calcium phosphate (Si-CaP) compared with autograft to generate solid lumbar fusion. STUDY DESIGN: Comparison of healing of instrumented posterolateral lumbar fusion in ewes at 2 and 6 months using Si-CaP or iliac crest autograft. METHODS: Eighteen skeletally mature ewes underwent implantation of either autograft or Si-CaP in the space spanning the L4-L5 transverse process. In vivo quantitative computed tomography (CT) scans were made at 2-month intervals and after euthanasia. Harvested spine segments were radiographed and biomechanically tested in bending at 6 months. Histological assessments were made at 2 and 6 months. RESULTS: Animals receiving Si-CaP graft were biomechanically and radiographically equivalent to those receiving autograft. Fusion mass density and volume were higher for the Si-CaP group throughout the healing period. Si-CaP regenerated normal bone tissue morphology, cellularity, and maturation with no inflammatory responses despite the fact that no autograft, bone marrow aspirate, or blood was mixed with the material. Histomorphometrically, fusion mass was higher for Si-CaP and bony bridging was equivalent when compared with autograft treatment. CONCLUSIONS: Si-CaP was biomechanically, radiographically, and histologically equivalent to autograft in generating a solid, bony, intertransverse process fusion in an ovine model. Both treatment groups achieved 100% bridging fusion after 6 months of healing.     

The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion

STUDY DESIGN: A posterolateral lumbar arthrodesis animal model using coralline hydroxyapatite as a bone graft substitute. OBJECTIVE: To determine the effectiveness of coralline hydroxyapatite as a bone graft substitute for lumbar spine fusion when used with bone marrow, autogenous bone graft, or an osteoinductive bone protein extract. SUMMARY OF BACKGROUND DATA: Coralline hydroxyapatite is commonly used as a bone graft substitute in metaphysial defects but its use in a more challenging healing environment such as the posterolateral spine remains controversial. There are no published animal studies in which the use of coralline hydroxyapatite has been evaluated in a posterolateral lumbar arthrodesis model. METHODS: Single-level posterolateral lumbar arthrodesis was performed at L5-L6 in 48 adult New Zealand White rabbits. Rabbits were assigned to one of three groups based on the graft material they received: 3.0 mL coralline hydroxyapatite 1.5 mL plus bone marrow; 1.5 mL coralline hydroxyapatite plus 1.5 mL autogenous iliac crest bone; and, 3.0 mL coralline hydroxyapatite plus 500 micrograms bovine-derived osteoinductive bone protein extract on each side. Rabbits were killed after 2, 5, or 10 weeks, and the spines were excised and evaluated by manual palpation, radiographs, tensile biomechanical testing, and nondecalcified histology. RESULTS: Fusions were assessed by manual palpation at 5 weeks for comparisons among the three groups of graft materials. The coralline hydroxyapatite used with bone marrow produced no solid fusions (0/14). When combined with an equal amount of autogenous iliac crest bone, coralline hydroxyapatite resulted in solid fusion in 50% (7/14) of the rabbits (P < 0.05). When combined with the osteoinductive growth factor extract, the coralline hydroxyapatite resulted in solid fusion in 100% (11/11) of the rabbits (P < 0.05). The fusion masses in the growth factor group were significantly stronger (1.8 +/- 0.2 vs. 1.3 +/- 0.1; P = 0.02) and stiffer (1.5 +/- 0.2 vs. 1.2 +/- 0.1, P = 0.04) based on tensile testing to failure when normalized to the adjacent unfused level. CONCLUSION: These data indicate that coralline hydroxyapatite with bone marrow was not an acceptable bone graft substitute for posterolateral spine fusion. When combined with autogenous iliac crest bone graft-coralline hydroxyapatite served as a graft extender yielding results comparable to those obtained with autograft alone. Coralline hydroxyapatite served as an excellent carrier for the bovine osteoinductive bone protein extract yielding superior results to those obtained with autograft or bone marrow.     

rhBMP-2 enhancement of posterolateral spinal fusion in a rabbit model in the presence of concurrently administered doxorubicin.

BACKGROUND CONTEXT: Spinal fusions can be necessary in patients undergoing chemotherapy with doxorubicin. In a previous study, doxorubicin was shown to decrease spinal fusion rates in a rabbit model of lumbar intertransverse process spinal fusion with autograft iliac crest bone. In the current study, we determine whether spinal fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2) can overcome the inhibitory effect of doxorubicin in spinal fusion. PURPOSE: To determine if rhBMP-2 can overcome the inhibitory effects of doxorubicin (adriamycin) in an animal model of posterolateral spinal fusion. STUDY DESIGN/SETTING: Prospective, controlled, rabbit model of posterolateral lumbar fusion. OUTCOME MEASURES: Spine fusion was assessed by manual palpation (by observers blinded to the treatment group) at the level of arthrodesis. Fusion was graded according to a five-tiered classification (0-4). Posteroanterior radiographs of the excised spines were also graded in a blinded fashion using a six-point scoring system (0-5) devised to describe the amount of bone observed between the L5-L6 transverse processes. METHODS: Thirty-two New Zealand White rabbits underwent posterolateral fusion at L5-L6 with either autograft (iliac crest autograft bone) or rhBMP-2 (rhBMP-2/absorbable collagen sponge (0.86 mg/level). All animals received a dose of doxorubicin (2.5 mg/kg) known to inhibit spine fusion via the central vein of the ear immediately postoperatively. Five weeks postoperatively the rabbits were euthanized. Spine fusion was assessed by manual palpation, and graft quality was assessed with posteroanterior radiographs. RESULTS: Four of the 16 spines (25%) in the autograft group and 16 of the 16 spines (100%) in the rhBMP-2 group fused in the presence of doxorubicin administration (p<.05). There was significantly increased bone formation in the rhBMP-2 group (p<.05). One unilateral, subclinical wound infection was observed in each group at the time of euthanization (autograft [n=1, 6%] and rhBMP-2 [n=1, 6%]). CONCLUSIONS: We confirm that when autograft is used, doxorubicin decreases spinal fusion rate (25%) compared with historical controls (60-75%). More importantly, using rhBMP-2 overcomes the inhibitory effect of doxorubicin, resulting in 100% fusion in our animal model. This study suggests that rhBMP-2 has the potential to improve fusion rates in human patients undergoing chemotherapy with doxorubicin.     

Mechanical and histologic evaluation of Collagraft in an ovine lumbar fusion model

The purpose of this study was to determine the effectiveness of a composite material composed of Type I bovine dermal collagen, 65% hydroxyapatite, and 35% tricalcium phosphate ceramic (Collagraft Bone Graft Matrix Strip NeuColl Incorporated, Palo Alto, CA) as a bone graft substitute for spinal fusion with and without the use of autologous bone marrow in an ovine lumbar spine model with pedicle screw fixation. Twenty-four adult sheep underwent a single level posterolateral (intertransverse process) L3-L4 lumbar fusion with one of three graft materials combined with rigid pedicle screw fixation. The three graft materials were Collagraft, Collagraft with marrow, and autogenous corticocancellous bone graft. Animals were euthanized 6 months after surgery and evaluated using dual energy x-ray absorptiometry, radiographs, histologic analysis, and mechanical testing. Dual energy xray absorptiometry between the transverse processes revealed that the mineral densities for the two Collagraft groups were significantly higher than the autogenous bone graft group. Histologic analysis confirmed that Collagraft was highly compatible and was well incorporated into the fusion mass. Both Collagraft groups had thick trabeculae and a mixture of lamellar and plexiform bone. The autogenous bone graft group had a smaller fusion complex, composed primarily of lamellar bone with thinner and fewer trabeculae. All three groups had similar mechanical properties. These results support the use of Collagraft in spinal fusion with pedicle screw fixation.     

Single-level lumbar spine fusion: a comparison of anterior and posterior approaches

This study is a retrospective review of 122 patients who underwent single-level lumbar spine fusion. The objectives were to directly compare perioperative morbidity and early results of single-level anterior interbody posterolateral intertransverse process lumbar spine fusion and to provide objective findings that may be useful in selecting surgical method. Lumbar spinal fusion is a well-recognized surgical treatment of intractable low back pain resulting from DDD or spondylolisthesis. Assessments of techniques, results, and outcomes have been published, but detailed head-to-head comparisons of anterior posterior approaches with objective operative and postoperative data are not available in the literature. A retrospective review of 122 patients who underwent either an anterior interbody or posterolateral intertransverse process (average follow-up 22 and 26 months, respectively) single-level instrumented lumbar spinal fusion was performed. Surgical, perioperative, and follow-up data were obtained directly from medical records. The findings compared included estimated blood loss, need for blood transfusion, number of units transfused, operative time, number of days in hospital, need for transitional facility care, complications, need for further surgery, radiographic fusion, and clinical results. There was significantly less blood loss, need for transfusion, amount of blood transfused, operative time, and hospital stay for patients with anterior fusion procedures (p < 0.01). There was no significant difference in need for transitional facility care, complication rates, and given follow-up period in radiographic fusion rate and clinical outcome. Clinical results were significantly worse for those undergoing revision primary fusion (p < 0.01). The anterior approach to single-level lumbar fusion is associated with less morbidity than the posterolateral approach. This may in turn affect surgical outcome and hospital cost. However, both approaches to single-level lumbar fusion produce similar early fusion rates and clinical results. Revision fusions had poor early results regardless of approach.     

Hydroxyapatite-bioactive glass ceramic composite as stand-alone graft substitute for posterolateral fusion of lumbar spine: a prospective, matched, and controlled study

STUDY DESIGN: Prospective, matched, and controlled study. OBJECTIVE: To evaluate the efficacy of hydroxyapatite-bioactive glass ceramic composite (Chitra-HABg) as a stand-alone graft substitute in promoting posterolateral fusion in the lumbar spine as compared with autologous bone. BACKGROUND: The use of ceramics as stand-alone graft substitutes in posterolateral fusion remains controversial. The Chitra-HABg is a new composite that has undergone clinical trials in various orthopedic applications with excellent clinical and radiologic outcomes. METHODS: Twenty-four patients underwent instrumented posterolateral fusion, with Chitra-HABg laid on the left intertransverse bed and autogenous graft on the right side. The primary outcome measure was radiologic consolidation of the graft, and secondary outcome measures were the work status and the Modified Oswestry Disability index. The McNamara and Student chi test were applied for statistical analysis. RESULTS: Although the study was prematurely terminated owing to the high incidence of resorption of Chitra-HABg, 22 of the 24 subjects were followed-up for a minimum of 1 year. At the end of 1-year, excellent radiologic outcome was seen on the right side (autogenous graft) in all the cases, whereas 95% (21/22) of the cases had poor consolidation on the left side (Chitra-HABg). The clinical outcome was rated as good in 16/22 (73%) patients, fair in 5, and poor in only 1 patient, but this had no statistically significant association with the consolidation of the fusion mass. CONCLUSIONS: This study clearly demonstrates that hydroxyapatite-bioactive glass ceramic composites (Chitra-HABg) has no role as stand-alone bone graft substitutes in posterolateral fusion of the lumbar spine, as the composite undergoes resorption without the formation of bridging callus. LEVEL OF EVIDENCE: Level 1.