Effect of zoledronic acid in an L6–L7 rabbit spine fusion model

Previous studies have shown that zoledronic acid administration can increase mineral content and strength in distraction osteogenesis. Of the few studies that have examined the use of bisphosphonates in spinal arthrodesis, none have assessed the effect of single dose treatment. The objective of this study was to evaluate the feasibility of enhancing spinal fusion rate using single dose zoledronic acid (ZA) to increase fusion-mass size and mineral density. Forty-eight New Zealand white rabbits underwent an L6–L7 intertransverse process fusion. The L6–L7 model is more challenging than the more commonly used level of L5–L6. Animals were randomly allocated to one of three groups, one received iliac crest bone graft alone, one group received iliac crest bone graft with locally administered zoledronic acid, 20 μg, and one group received iliac crest bone graft with a single dose of systemically administered zoledronic acid, 0.1 mg/kg. ZA doses were administered at the time of surgery. Twenty-four rabbits were culled at 6 weeks and 24 rabbits were culled at 12 weeks. Success of spinal fusion was determined by manual palpation. Specimens were evaluated radiographically, underwent quantitative computerised tomography analysis and were tested biomechanically in flexion and extension. In the six-week group, only five of the 24 spines fused with no noticeable trend with respect to treatment. In the 12-week group there was a trend toward increased fusion in the systemically administered ZA group (63%) versus the other two groups (25%) but was not statistically significant (p = 0.15). Radiographically, the local ZA treatment group showed a delay in remodelling with the presence of unremodelled bone chips. The 12-week systemic ZA group exhibited an 86% increase in BMC, a 31% increase in vBMD and a 41% increase in the volume of the fusion-mass (p < 0.05). The 12-week local ZA group also showed significant increases in BMC (69%), vBMD (31%) and total fusion-mass volume (29%) (p < 0.05). Biomechanical testing showed that the range of motion in flexion decreased to 4.5 (±2.5) degrees and 4.8 (±4.7) degrees for the local and systemic groups respectively compared to 9.6 (±4.9) degrees for the control group (p < 0.05). This study has shown that zoledronic acid increased fusion-mass size and bone mineral content. Systemic ZA led to an increased fusion rate; however the fusion rate remained below 100%. We suggest that bisphosphonate treatment may require an anabolic conjunctive therapy to ensure enhanced successful fusion.     

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 versus allograft with or without demineralized bone matrix in posterolateral lumbar fusion in rabbits. Laboratory investigation

OBJECT: Posterolateral spinal fusions are performed to treat different spinal disorders. Autograft continues to be the gold standard; it is, however, associated with donor site morbidity and limited sources. Allograft has been used, but has been reported to result in lower fusion rates. Demineralized bone matrix (DBM) has also been used and reportedly increases the fusion rate in a variety of critical defect models. Different forms of DBM are available, not all have been independently studied. To evaluate the effect of a xenogenic DBM added to allograft on the fusion rate of posterolateral lumbar spine arthrodesis the authors designed an experimental study comparing posterolateral fusion rate using autograft, allograft, and allograft plus a xenogenic DBM in a validated animal model. METHODS: A bilateral, 1-level (L4-5) intertransverse process fusion was performed in 45 male New Zealand rabbits. Iliac crest bone graft was harvested bilaterally from each rabbit. The rabbits were randomly assigned to 3 groups: Group I, Autograft, 15 rabbits; Group II, Allograft, 15 rabbits; and Group III, Allograft plus DBM in a paste form (Dynagraft). The animals were killed 8 weeks after surgery. Fusion was assessed radiographically and by manual palpation by 2 independent observers. The results were analyzed using the Fisher exact test and chi-square test. RESULTS: The fusion rate was 46.6% (7 of 15 rabbits) in the autograft group, 33.3% (5 of 15 rabbits) in the allograft group, and 33.3% (5 of 15 rabbits) in the allograft plus DBM group (p > 0.05). CONCLUSIONS: Autograft produced a higher fusion rate than allograft in this spinal fusion rabbit model, but the difference was not statistically significant. Allograft plus xenogenic DBM showed the same fusion rate as allograft alone.     

The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model. Laboratory investigation

OBJECT: Several reports have shown that nonsteroidal antiinflammatory drugs (NSAIDs) have an inhibitory effect in osteogenesis and reduce heterotopic ossification in humans. A deleterious effect of NSAIDs in posterolateral intertransverse process fusion has also been suggested. The authors used a validated rabbit model to try to determine the influence of the NSAID ketoprophen on the fusion rate in lumbar spinal arthrodesis. METHODS: Thirty New Zealand male rabbits underwent posterolateral (intertransverse process) bilateral spinal fusions at a single level, using autologous bone graft obtained from both iliac crests. The animals were randomized after the operation, so that 15 rabbits received ketoprophen as a postoperative analgesic and the other 15 received the postoperative analgesic tramadol. The animals were killed 8 weeks after surgery, and fusion status was determined by inspection, palpation, anteroposterior radiographs, and histological analysis. RESULTS: A solid fusion was obtained in eight rabbits (53%), and pseudarthrosis in seven rabbits (47%) in each group. CONCLUSIONS: These findings suggest that the use of ketoprophen after intertransverse spinal fusion at a single level does not decrease the fusion rate, compared with tramadol.     

Murine models of posterolateral spinal fusion: A systematic review

BackgroundRodent models are commonly used experimentally to assess treatment effectiveness in spinal fusion. Certain factors are associated with better fusion rates. The objectives of the present study were to report the protocols most frequently used, to evaluate factors known to positively influence fusion rate, and to identify new factors.MethodA systematic literature search of PubMed and Web of Science found 139 experimental studies of posterolateral lumbar spinal fusion in rodent models. Data for level and location of fusion, animal strain, sex, weight and age, graft, decortication, fusion assessment and fusion and mortality rates were collected and analyzed.ResultsThe standard murine model for spinal fusion was male Sprague Dawley rats of 295 g weight and 13 weeks’ age, using decortication, with L4-L5 as fusion level. The last two criteria were associated with significantly better fusion rates. On manual palpation, the overall mean fusion rate in rats was 58% and the autograft mean fusion rate was 61%. Most studies evaluated fusion as a binary on manual palpation, and only a few used CT and histology. Average mortality was 3.03% in rats and 1.56% in mice.ConclusionsThese results suggest using a rat model, younger than 10 weeks and weighing more than 300 grams on the day of surgery, to optimize fusion rates, with decortication before grafting and fusing the L4-L5 level.     

In vivo evaluation of calcium sulfate as a bone graft substitute for lumbar spinal fusion

BACKGROUND CONTEXT: Posterolateral fusions of the lumbar spine have nonunion rates as high as 35%. The availability of autologous bone to promote fusion is limited, particularly for multilevel fusions. Bone substitutes have been proposed to augment or replace autologous bone for spinal surgery. Calcium sulfate offers high porosity, osteoconductivity, and high resorption rate. This material has been used successfully for treatment of long bone defects but has not been investigated as a bone graft substitute for spinal fusions. PURPOSE: To determine whether the use of calcium sulfate granules in conjunction with an implantable electrical stimulator is a safe and effective means of attaining spinal fusion. STUDY DESIGN/SETTING: A rabbit lumbar fusion model was used to assess a calcium sulfate bone graft substitute in combination with electrical stimulation for spinal fusion. METHODS: Thirty-six adult New Zealand White female rabbits were divided into three groups. Each group underwent a single-level (L5-L6) fusion, receiving 3.0 cc calcium sulfate granules with bone marrow aspirate from the iliac crest. Group 1 had no electrical stimulator applied. Groups 2 and 3 received a 40-microA (Group 2) or a 100-microA (Group 3) implantable electrical stimulator. The animals were sacrificed at 8 weeks, and the rabbit spines were subjected to radiographic assessment, manual palpation, and mechanical testing. RESULTS: Two rabbits died postoperatively. The radiographic assessment revealed no fusions occurred at the adjacent nonoperated control levels (L4-L5). There were no fusions observed within Group 1, containing the calcium sulfate and bone marrow aspirate alone. The sites with the implantable stimulators showed a dose-dependent increase in fusion stiffness. However, no fusion mass in Group 2 or 3 was graded as bilaterally complete. CONCLUSION: This study found that calcium sulfate as a bone graft substitute was unsuccessful in promoting spine fusion in a rabbit model. There was radiographic evidence of rapid resorption of the calcium sulfate within 4 weeks after surgery. The use of electrical stimulation created a dose-dependent increase in mechanical competence of the bony mass. However, the addition of direct current (DC) current did not significantly alter fusion rates with calcium sulfate used as the bone graft substitute in this model.     

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.     

Application of extracorporeal shock wave treatment to enhance spinal fusion: a rabbit experiment

BACKGROUND: Extracorporeal shock wave treatment has been used to treat many orthopedic disorders. However, the effect of extracorporeal shock waves on spinal fusion has not been reported. METHODS: Fifteen rabbits were used in this study. Spinal fusion was performed with decortication of bilateral L5 and L6 transverse processes, and placement of the bone chips onto the ipsilateral L5-L6 intertransverse space. The right L5 and L6 transverse processes in all animals were treated with 1000 impulses of ESWT at 14 kV (equivalent to 0.18 mJ/mm(2)) at 3 and 6 weeks after surgery. The left transverse processes did not receive ESWT, and were served as controls. Radiographic examinations of the spines were performed at 3, 6, and 12 weeks. Computed tomography was performed at 12 weeks. The rabbits were killed at 12 weeks, and the spinal segments were harvested for histomorphological examination. RESULTS: Radiographs of the tested rabbits taken at different post-ESWT stages demonstrated repairing effect of ESWT on the fusion gap of the treated (right) sides. Statistical analysis of the image studies indicated that 11 (73%) of 15 rabbits showed superior fusion mass on the ESWT (right) side than that of control (left) side (P < .001). The remaining 4 (27%) rabbits showed no discernable fusion difference between the ESWT side and the control side. Histomorphological examination showed good new bone formation in 9 fusion masses. All of these cases were noted on the ESWT (right) sides. Statistical analysis showed that ESWT sides had better new bone formation than the control sides (P = .001). CONCLUSIONS: Results of this study demonstrated that ESWT is effective in promoting spinal fusion in rabbits.     

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.     

The effects of doxorubicin (adriamycin) on spinal fusion: an experimental model of posterolateral lumbar spinal arthrodesis

BACKGROUND CONTEXT: Malignant spinal lesions may require surgical excision and segmental stabilization. The decision to perform a concomitant fusion procedure is influenced in part by the need for adjunctive chemotherapy as well as the patient's anticipated survival. Although some evidence exists that suggests that chemotherapy may inhibit bony healing, no information exists regarding the effect of chemotherapy on spinal fusion healing. PURPOSE: To determine the effect of a frequently used chemotherapeutic agent, doxorubicin, on posterolateral spinal fusion rates. STUDY DESIGN/SETTING: Prospective animal model of posterolateral lumbar fusion. OUTCOME MEASURES: Determination of spinal fusion by manual palpation of excised spines. Plain radiographic evaluation of denuded spines to evaluate intertransverse bone formation. METHODS: Thirty-two New Zealand White rabbits underwent posterior intertransverse process fusion at L5-L6 with the use of iliac autograft bone. Rabbits randomly received either intravenous doxorubicin (2.5 mg/kg) by means of the central vein of the ear at the time of surgery (16 animals) or no treatment (16 animals; the control group). The animals were euthanized at 5 weeks, and the lumbar spines were excised. Spine fusion was assessed by manually palpating (by observers blinded to the treatment group) at the level of arthrodesis, and at the adjacent levels proximal and distal. This provided similar information to surgical fusion assessment by palpation in humans. Fusion was defined as the absence of palpable motion. Posteroanterior radiographs of the excised spines were graded in a blinded fashion using a five-point scoring system (0 to 4) devised to describe the amount of bone observed between the L5-L6 transverse processes. Power analysis conducted before initiation of the study indicated that an allocation of 16 animals to each group would permit detection of at least a 20% difference in fusion rates with statistical significance at p=.05. RESULTS: Eleven of the 16 spines (69%) in the control group and 6 of the 16 spines (38%) in the doxorubicin group fused. This difference was statistically significant (=.038). There was no significant correlation (p>.05) between the radiographic grade of bone formation (0 to 4) and fusion as determined by palpation. There were four wound infections in the control group and four in the doxorubicin group. However, solid fusions were palpated in three of these four spines in both the control and treatment groups. CONCLUSIONS: No significant differences in wound complications were noted with doxorubicin administration. A single dose of doxorubicin administered intravenously at the time of surgery appears to play a significant inhibitory role in the process of spinal fusion. If similar effects occur in humans, these data suggest that doxorubicin may be harmful to bone healing in a spine fusion if given during the perioperative period. Further investigation will be necessary to determine the effect of time to aid at determining whether doxorubicin administered several weeks pre- or postoperatively results in improved fusion rate, and whether bone morphogenetic proteins can overcome these inhibitory effects.     

Manipulation of anabolic and catabolic responses with bone morphogenetic protein and zoledronic acid in a rat spinal fusion model

Bone fusion involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the surgical site. It has been reported that systemically administering a single dose of zoledronic acid (ZA) at the optimal time increases the strength of the bone morphogenetic protein (BMP)–mediated callus. In the present study, we aimed to investigate the effect of BMP-2 and ZA in a rat spinal model. Sixty-seven rats were divided into 6 groups: group I (n = 11) animals were implanted with a carrier alone, group II (n = 12) animals were implanted with a carrier and a subcutaneous injection of ZA was administered 2 weeks after surgery, group III (n = 12) animals were implanted with a carrier containing 1 μg of rhBMP-2, group IV (n = 12) animals were implanted with a carrier containing 1 μg of rhBMP-2 and a subcutaneous injection of ZA was administered 2 weeks after surgery, group V (n = 10) animals were implanted with a carrier containing 3 μg of rhBMP-2, and group VI (n = 10) animals were implanted with a carrier containing 3 μg of rhBMP-2 and a subcutaneous injection of ZA was administered 2 weeks after surgery. The rats were euthanized after 6 weeks, and their spines were explanted and assessed by manual palpation, radiography, high-resolution micro-computerized tomography (micro-CT), and histologic analysis. The fusion rates in group VI (60%) were considerably higher than those in the groups I (0%), II (0%), III (12.5%), IV (20.8%), and V (35%), (P < 0.05). Additionally, the radiographic scores of group VI were higher than those in the other groups, (P < 0.05). In micro-CT analysis, the tissue and bone volumes of the callus were significantly higher in group VI than those in the other groups, (P < 0.05). The trabecular number was significantly higher and the trabecular spacing was significantly lower in group VI than those in the other groups, (P < 0.05). The combination of rhBMP-2 and ZA administered systemically as a single dose at the optimal time was efficacious in our rat spinal fusion model. Our results suggest that this combination facilitates spinal fusion and has potential clinical application.     

The effect of anti-resorptive therapies on bone graft healing in an ovariectomized rat spinal arthrodesis model

Bone grafting is commonly used to treat skeletal disorders associated with a large bone defect or unstable joint. Spinal arthrodesis surgery, which is the most common application of bone graft, is performed in the elderly and anti-resorptive therapy is sometimes started postoperatively in patients with bone fragility due to osteoporosis, despite insufficient knowledge about the effects of these drugs on bone graft healing. Therefore, we studied the effect of bisphosphonates (BP) and selective estrogen receptor modulators (SERM) on bone graft healing in an ovariectomized rat spinal arthrodesis model. Female Sprague-Dawley rats (n=100) were ovariectomized or sham-operated, and randomized into four groups: Sham (sham-operated+vehicle), Ovx (ovariectomy+vehicle), Ovx-Rlx (ovariectomy+raloxifene, 1 mg/kg/day), and Ovx-Aln (ovariectomy+alendronate, 0.01 mg/kg/day). Four weeks after ovariectomy, lumbar spinal arthrodesis surgery was performed using an autologous bone graft. Animals were killed 2, 4, and 8 weeks after surgery, and fusion assessment, three-dimensional micro-computed tomography, histomorphometry, mRNA expression analysis, and serum bone metabolic marker analysis were performed. The results indicated that neither BP nor SERM significantly altered the fusion rate, but the bone graft healing process was differentially affected. BP inhibited endochondral ossification and graft bone resorption, but induced the growth of a larger, denser fusion mass compared to Ovx by strongly suppressing osteoclastic activity. SERM mildly suppressed bone remodeling, but did not significantly inhibit the ossification process, leading to a fusion mass comparable with that of Sham animals. These findings suggested that spinal fusion surgery outcome is not likely to be altered by BP or SERM treatment started immediately after spinal arthrodesis surgery; however, to avoid adverse effects of BP on bone graft healing, BP treatment should be delayed during the immediate postoperative period.     

Direct current stimulation for spine fusion in a nicotine exposure model.

BACKGROUND CONTEXT: Decreased effectiveness in spinal fusion procedures in patients who smoke before, during, or after the operation has been noted in several clinical studies. In previous work, direct current (DC) electrical stimulation has been shown to enhance inter-transverse process fusion in a rabbit model. PURPOSE: To test the efficacy of DC stimulation on bone healing in spinal fusion in rabbits exposed to nicotine. STUDY DESIGN/SETTING: A randomized and controlled interventional study. METHODS: Thirty male New Zealand white rabbits received a single level posterolateral, inter-transverse process fusion with autologous iliac crest bone. One group (control) acted as a control without nicotine or electrical stimulation. A second group (Nic) received a continuous dose of nicotine via a transdermal patch to simulate a heavy smoker, and a third group, nicotine/stimulator group (Nic/Stim), additionally received a 100-microamp DC stimulator. The fusion masses (L5-L6) and the adjacent unfused control segment (L4-L5) were evaluated radiographically, manually, and biomechanically. RESULTS: The Nic group showed significantly higher fusion rate compared with the control group. The Nic/Stim group also demonstrated significantly higher fusion rate and X-ray trabeculation compared with the control group. However, the Nic/Stim group was not significantly higher than the Nic group in fusion rate or X-ray trabeculation. CONCLUSIONS: Nicotine significantly improved fusion rate compared with controls, and DC stimulation significantly increased X-ray trabeculation of nicotine treated rabbits compared with controls.     

Evaluation of a new formulation of demineralized bone matrix putty in a rabbit posterolateral spinal fusion model

Background contextAlternatives to autologous bone graft (ABG) with osteoconductive, osteoinductive, and osteogenic potential continue to prove elusive. Demineralized bone matrix (DBM) however, with its osteoconductive and osteoinductive potential remains a viable option to ABG in posterolateral spine fusion.PurposeTo compare the efficacy of a new formulation of DBM putty with that of ABG in a rabbit posterolateral spinal fusion model.Study designEfficacy of a new formulation of DBM was studied in an experimental animal posterolateral spinal fusion model.MethodsTwenty-four male New Zealand White rabbits underwent bilateral posterolateral spine arthrodesis of the L5–L6 intertransverse processes, using either ABG (control group, n=12) or DBM (DBM made from rabbit bone) putty (test group, n=12). The animals were killed 12 weeks after surgery and the lumbar spines were excised. Fusion success was evaluated by manual palpation, high resolution X-rays, microcomputed tomography imaging, biomechanical four-point bending tests, and histology.ResultsTwo animals were lost because of anesthetic related issues. Manual palpation to assess fusion success in the explanted lumbar spines showed no statistical significant difference in successful fusion in 81.8% (9/11) of DBM group and 72.7% (8/11) of ABG group (p=.99). Reliability of these assessments was measured between three independent observers and found near perfect agreement (intraclass correlation cofficient: 0.92 and 0.94, respectively). Fusion using high resolution X-rays was solid in 10 of the DBM group and 9 of the ABG group (p=.59). Biomechanical testing showed no significant difference in stiffness between the control and test groups on flexion, extension, and left lateral and right lateral bends, with p values accounting for .79, .42, .75, and .52, respectively. The bone volume/total volume was greater than 85% in the DBM treated fusion masses. Histologic evaluation revealed endochondral ossification in both groups, but the fusion masses were more mature in the DBM group.ConclusionsThe DBM putty achieved comparable fusion rates to ABG in the rabbit posterolateral spinal fusion model.     

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.     

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.     

Experimental study of osteoplastic laminectomy in the lumbar spine of rabbits

Osteoplastic laminectomy has been used to treat lumbar canal stenosis and to prevent postoperative lumbar spinal instability by reconstructing the posterior element of the lumbar spine, which has been documented in many clinical studies. However, the biological sequence of repairing the posterior lumbar element, which is replaced at the time of surgery, has not yet been made clear. An in vivo rabbit study was designed to observe the biological sequence of repairing the replaced posterior element of the lumbar spine. Twenty-one adult rabbits underwent osteoplastic laminectomy at the L6. Animals were killed at 2, 4, 8, 12, 26, and 52 weeks after surgery. The samples of the L6 vertebra, which contained the replaced lamina and spinous process, were analyzed by radiography, computed tomography (CT), and a histological method. Overall, radiograms demonstrated clearly the union of interarticular osteotomized sites from 4 to 8 weeks. CT findings revealed that the union of interarticular osteotomized sites could be confirmed beginning at 12 weeks, and that postoperative narrowing of the lumbar spinal canal had not occurred in the rabbit model. The biological sequence of repairing the replaced lamina and spinous process was characterized by slowly progressive creeping substitution, with continuous remodeling.     

Opioids delay healing of spinal fusion: a rabbit posterolateral lumbar fusion model

Background Context

Opioid use is prevalent in the management of pre- and postoperative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in vitro, and a previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans.

Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion model

We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p<0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p<0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer.     

Posterior spinal fusion in adolescent idiopathic scoliosis with or without intraoperative cell salvage system: a retrospective comparison

This study investigates efficacy and safety of routine cell salvage system use in adolescent idiopathic scoliosis patients undergoing primary posterior spinal fusion surgery with segmental spinal instrumentation. Forty-five consecutive adolescent idiopathic scoliosis patients undergoing posterior spinal fusion by two surgeons at a single hospital were studied. Intraoperative cell salvage system was used in 23 patients, and the control group was 22 patients who underwent surgery without cell salvage system. The cell salvage system was the Haemonetics Cell Saver 5. The primary outcome measures were intraoperative and perioperative allogeneic transfusion rate, difference between preoperative and discharge Hg and Hct levels. Average patient age was 14.65 ± 1.49 in cell saver group and 13.86 ± 2.0 in control group. In cell saver group, average intraoperative autotransfusion was 382.1 ± 175 ml. Average perioperative allogeneic blood transfusion need was 1.04 ± 0.7 unit in cell saver group and 2.5 ± 1.14 unit in control group. No transfusion reactions occurred in either group. Average hemoglobin level in cell saver group was 10.7 ± 0.86 and average hemoglobin level in control group was 10.7 ± 0.82 on discharge. Cell saver reduces perioperative transfusion rate in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis.