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Micheal Raad, Jay S. Reidler, Mostafa H. El Dafrawy, Raj M. Amin, Amit Jain, Brian J. Neuman, Lee H. Riley III, Daniel M. Sciubba, Khaled M. Kebaish and Richard L. Skolasky

L umbar spinal stenosis (LSS) is often a debilitating condition that is associated with substantial pain and disability related to degenerative bony overgrowth impinging on neural structures in the lumbar spine. The primary goal of LSS surgery is to decompress the compromised neural structures. Several studies have reported similar or superior long-term outcomes after surgical decompression compared with nonoperative treatment in LSS patients who were candidates for surgery. 2 , 10 , 14 , 22 However, the role of spinal arthrodesis in these patients is more

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Tobias Ludwig do Nascimento, Guilherme Finger, Ericson Sfreddo, André Martins de Lima Cecchini, Felipe Martins de Lima Cecchini and Marco Antônio Stefani

has been steadily increasing, especially S. aureus . 17 In a recent large retrospective cohort study of 37 children’s hospitals, McLeod et al. found that broad-spectrum coverage for gram-negative organisms and MRSA was used in 37% of adolescent idiopathic scoliosis cases and 52% of neuromuscular scoliosis cases. 13 Topical vancomycin, which has been proven safe, 2 , 14 , 15 has been used since 2011 to reduce postoperative infection rates 1 , 2 , 5 , 6 , 9 , 10 , 12 , 15 , 18 , 19 , 22–24 and has been recommended in some spinal arthrodesis guidelines. 16 However

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Nancy Abu-Bonsrah, C. Rory Goodwin, Gezzer Ortega, Fizan Abdullah, Edward Cornwell, Rafael De la Garza-Ramos, Mari L. Groves, Michael Ain, Paul D. Sponseller and Daniel M. Sciubba

S pinal arthrodesis is commonly performed in the pediatric population for a number of indications, including pediatric deformity, trauma, and tumor-induced instability. 1 , 2 , 5 , 7 , 10 , 13 , 14 , 16 , 17 , 23–25 Patients undergoing spinal arthrodesis are at significant risk for developing complications and having unplanned readmissions and/or reoperations. These clinical outcomes are undesirable for patients, physicians, and the health care system in general, as they can result in increased cost and decreased quality of life. Greater understanding of the

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Gregory A. Helm, Tord D. Alden, Elisa J. Beres, Sarah B. Hudson, Subinoy Das, Jonathan A. Engh, Debra D. Pittman, Kelvin M. Kerns and David F. Kallmes

addition to being involved in skeletal histogenesis, are also intricately involved in the development of the brain, spinal cord, liver, kidneys, skeletal muscle, eyes, and epithelium. 8, 32, 41 However, the osteogenic properties of several of the BMPs have attracted the greatest research interest, and significant efforts are currently underway to advance their use in the clinical setting. 31 Human recombinant BMP-2 and BMP-7, when applied on a collagen sponge, have been shown to promote spinal arthrodesis in rodents, rabbits, dogs, and primates. 3, 5, 10, 14, 20, 21

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Christoph P. Hofstetter, Anna S. Hofer and Allan D. Levi

morphogenetic protein (BMP), a prototypical osteoinductive protein belonging to the superfamily of transforming growth factor-beta, 21 , 46 was first discovered in 1965 by Marshall R. Urist. 85 Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been tested clinically for use in spinal arthrodesis in several prospective, randomized clinical trials beginning in 1997. Clinical studies of lumbar 11 , 48 and cervical fusion 4 in humans have demonstrated consistent osteoinduction mediated by rhBMP-2-impregnated absorbable collagen sponges (INFUSE) placed into

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Paul D. Sawin, Curtis A. Dickman, Neil R. Crawford, M. Stephen Melton, William D. Bichard and Volker K. H. Sonntag

Object. The use of corticosteroid agents during the healing phase after spinal arthrodesis remains controversial. Although anecdotal opinion suggests that corticosteroids may inhibit bone fusion, such an effect has not been substantiated in clinical trials or laboratory investigations. This study was undertaken to delineate the effect of exogenous corticosteroid administration on bone graft incorporation in an experimental model of posterolateral lumbar fusion.

Methods. An established, well-validated model of lumbar intertransverse process spinal fusion in the rabbit was used. Twenty-four adult New Zealand white rabbits underwent L5–6 bilateral posterolateral spinal fusion in which autogenous iliac crest bone graft was used. After surgery, the animals were randomized into two treatment groups: a control group (12 rabbits) that received intramuscular injections of normal saline twice daily and a dexamethasone group (12 rabbits) that received intramuscular dexamethasone (0.05 mg/kg) twice daily. After 42 days, the animals were killed and the integrity of the spinal fusions was assessed by radiography, manual palpation, and biomechanical testing.

In seven (58%) of the 12 control rabbits, solid posterolateral fusion was achieved. In no dexamethasone-treated rabbits was successful fusion achieved (p = 0.003). Tensile strength and stiffness of excised spinal segments were significantly lower in dexamethasone-treated animals than in control animals (tensile strength 91.4 ± 30.6 N and 145.3 ± 48.2, respectively, p = 0.004; stiffness 31.4 ± 11.6 and 45.0 ± 15.2 N/mm, respectively, p = 0.02).

Conclusions. The corticosteroid agent dexamethasone inhibited bone graft incorporation in a rabbit model of single-level posterolateral lumbar spinal fusion, inducing a significantly higher rate of nonunion, compared with that in saline-treated control animals.

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Gregory A. Helm, Hayan Dayoub and John A. Jane Jr.

In the prototypical method for inducing spinal fusion, autologous bone graft is harvested from the iliac crest or local bone removed during the spinal decompression. Although autologous bone remains the “gold standard” for stimulating bone repair and regeneration, modern molecular biology and bioengineering techniques have produced unique materials that have potent osteogenic activities. Recombinant human osteogenic growth factors, such as bone morphogenetic proteins, transforming growth factor–β, and platelet-derived growth factor are now produced in highly concentrated and pure forms and have been shown to be extremely potent bone-inducing agents when delivered in vivo in rats, dogs, primates, and humans. The delivery of pluripotent mesenchymal stem cells (MSCs) to regions requiring bone formation is also compelling, and it has been shown to be successful in inducing osteogenesis in numerous pre-clinical studies in rats and dogs. Finally, the identification of biological and nonbiological scaffolding materials is a crucial component of future bone graft substitutes, not only as a delivery vehicle for bone growth factors and MSCs but also as an osteoconductive matrix to stimulate bone deposition directly. In this paper, the currently available bone graft substitutes will be reviewed and the authors will discuss the novel therapeutic approaches that are currently being developed for use in the clinical setting.

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Donald D. Dietze Jr., M.D., Richard G. Fessler and R. Patrick Jacob

Primary reconstruction using bone grafts and instrumentation for spinal infections remains controversial. Between 1991 and 1993, 27 infections of the spinal column were treated at the Department of Neurosurgery of the University of Florida. Of the 27 cases 20 (six cervical, eight thoracic, and six lumbar spine) required surgical debridement and spinal reconstruction to maximize eradication of the infection and maintenance of spinal alignment. All of the cervical and lumbar cases were caused by bacterial infections, and two of eight thoracic cases were caused by tuberculous infections. Spinal arthrodesis was performed in all cases: interbody grafts were used in 18 procedures and posterolateral onlay grafts in 14. Interbody grafts were autologous in 10 cases (six rib and four iliac crest) and homoplastic in eight (six fibular and two humerus). All of the posterolateral onlay grafts were autologous (three rib and 11 iliac crest). Spinal instrumentation was used in 15 cases: four with Caspar plates and 11 with posterior segmental fixation (five hook/rod constructs and six screw/rod constructs). Seventeen of 20 patients achieved improved clinical status postoperatively and 18 of 20 showed radiographic evidence of bone fusion. Antibiotic drugs were administered parenterally for an average of 6 weeks followed by a 3-month course of oral antibiotic medications. Tuberculous infections were treated for 1 year with antibiotic therapy. The average follow-up period was 37 months from surgery and 31 months after completion of treatment with antibiotic drugs. The authors conclude that primary arthrodesis and instrumentation can be performed in acute spinal infections; however, successful management depends on aggressive debridement of infectious foci and prolonged treatment with parenteral antibiotic drugs.

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Donald D. Dietze Jr., Richard G. Fessler and R. Patrick Jacob

✓ Primary reconstruction using bone grafts and instrumentation for spinal infections remains controversial. Between 1991 and 1993, 27 infections of the spinal column were treated at the Department of Neurosurgery of the University of Florida. Of the 27 cases 20 (six cervical, eight thoracic, and six lumbar spine) required surgical debridement and spinal reconstruction to maximize eradication of the infection and maintenance of spinal alignment. All of the cervical and lumbar cases were caused by bacterial infections, and two of eight thoracic cases were caused by tuberculous infections. Spinal arthrodesis was performed in all cases: interbody grafts were used in 18 procedures and posterolateral onlay grafts in 14. Interbody grafts were autologous in 10 cases (six rib and four iliac crest) and allograft in eight (six fibular and two humerus). All of the posterolateral onlay grafts were autologous (three rib and 11 iliac crest). Spinal instrumentation was used in 15 cases: four with Caspar plates and 11 with posterior segmental fixation (five hook/rod constructs and six screw/rod constructs). Seventeen of 20 patients achieved improved clinical status postoperatively and 18 of 20 showed radiographic evidence of bone fusion. Antibiotic drugs were administered parenterally for an average of 6 weeks followed by a 3-month course of oral antibiotic medications. Tuberculous infections were treated for 1 year with antibiotic therapy. The after completion of treatment with antibiotic drugs. The authors conclude that primary arthrodesis and instrumentation can be performed in acute spinal infections; however, successful management depends on aggressive debridement of infectious foci and prolonged treatment with parenteral antibiotic drugs.

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Tord D. Alden, Gerald R. Hankins, Elisa J. Beres, David F. Kallmes and Gregory A. Helm

Gene therapy has many potential applications in neurosurgery. One application involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight glycoprotein that induces bone formation in vivo. Numerous studies have demonstrated that the BMP-2 protein can enhance spinal fusion. This study was undertaken to determine whether direct injection of an adenoviral construct containing the BMP-2 gene can be used for spinal fusion. Twelve athymic nude rats were used in this study. Recombinant, replication-defective type-5 adenovirus with a universal promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus constructed with a universal promoter and ß-galactosidase (ß-gal) gene (Ad-ß-gal) was used as a control. Seven and one-half microliters of virus was injected percutaneously and paraspinally at the lumbosacral junction in three groups (four animals each): 1) Ad-BMP-2 bilaterally, 2) Ad-BMP-2 on the right, Ad-ß-gal on the left, and 3) Ad-ß-gal bilaterally. Computerized tomography (CT) scans of the lumbosacral spine were obtained at 3, 5, and 12 weeks. At 12 weeks, the animals were killed for histological inspection. Ectopic bone formation was seen both on three-dimensional CT reconstruction and histologically in all rats at sites treated with Ad-BMP-2. Histological analysis revealed bone at different stages of maturity adjacent to the spinous processes, laminae, and transverse processes. This study clearly demonstrated that it is possible to produce in vivo endochondral bone formation by using direct adenoviral construct injection into the paraspinal musculature, which suggests that gene therapy may be useful for spinal fusion in the future.