Intravenous Ketorolac Substantially Reduces Opioid Use and Length of Stay After Lumbar Fusion: A Randomized Controlled Trial.

STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial. OBJECTIVE: To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A). SUMMARY OF BACKGROUND DATA: Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study. PATIENTS AND METHODS: Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours. RESULTS: A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A ( P = 0.025) and IV-P ( P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance ( P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst ( P = 0.004), best ( P = 0.001), average ( P = 0.001), and current pain ( P = 0.002) on postoperative day 1, and significantly shorter LOS ( P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates. CONCLUSIONS: By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of "enhanced recovery after surgery" protocols.

Inducing Angiogenesis in the Nucleus Pulposus.

Bone morphogenetic protein (BMP) gene delivery to Lewis rat lumbar intervertebral discs (IVDs) drives bone formation anterior and external to the IVD, suggesting the IVD is inhospitable to osteogenesis. This study was designed to determine if IVD destruction with a proteoglycanase, and/or generating an IVD blood supply by gene delivery of an angiogenic growth factor, could render the IVD permissive to intra-discal BMP-driven osteogenesis and fusion. Surgical intra-discal delivery of naïve or gene-programmed cells (BMP2/BMP7 co-expressing or VEGF165 expressing) +/- purified chondroitinase-ABC (chABC) in all permutations was performed between lumbar 4/5 and L5/6 vertebrae, and radiographic, histology, and biomechanics endpoints were collected. Follow-up anti-sFlt Western blotting was performed. BMP and VEGF/BMP treatments had the highest stiffness, bone production and fusion. Bone was induced anterior to the IVD, and was not intra-discal from any treatment. chABC impaired BMP-driven osteogenesis, decreased histological staining for IVD proteoglycans, and made the IVD permissive to angiogenesis. A soluble fragment of VEGF Receptor-1 (sFlt) was liberated from the IVD matrix by incubation with chABC, suggesting dysregulation of the sFlt matrix attachment is a possible mechanism for the chABC-mediated IVD angiogenesis we observed. Based on these results, the IVD can be manipulated to foster vascular invasion, and by extension, possibly osteogenesis.

Comparison of a fluoroscopic 3-dimensional imaging system and conventional CT in detection of pars fractures in the cadaveric lumbar spine.

STUDY DESIGN: Cadaveric Study. OBJECTIVE: To compare a fluoroscopic imaging system with computed tomography (CT) and radiographs in detection of spondylolysis and radiation exposure in a cadaver model. SUMMARY OF BACKGROUND DATA: Lumbar spondylolysis is defined as a defect or fracture of the pars interarticularis and occurs with or without anterior spondylolisthesis. CT scan is the gold standard imaging study for spondylolysis but is limited by the supine position, which may cause reduction of anterolisthesis and by ionizing radiation, which limits the frequency of follow-up scans. METHODS: Thirteen intact cadaveric lumbar spine segments with 26 pars were randomized to be left intact or to undergo simulated fracture using a 1.3 mm oscillating microsurgical saw. Fifteen pars underwent simulated fracture and 11 pars were left intact. Lumbar spine segments were imaged using plain radiographs, multiplanar fluoroscopic imaging, and conventional CT scan. The images were interpreted by 3 observers blinded to the number and location of defects. Radiation exposure and doses were recorded from all imaging units. RESULTS: Average radiation doses were 0.0025 mSv for each radiograph, 0.23 mSv (low dose) and 0.47 mSv (high dose) for fluoroscopic imaging, and 1.5 mSv for conventional CT imaging (pediatric dose setting). Evaluation of radiographs for spondylolysis had sensitivity of 98% and specificity of 97%. Evaluation using low-dose fluoroscopic images, high-dose fluoroscopic images, and CT scan images correctly identified the status of all pars based on multiplanar images; sensitivity and specificity were 100%. Kappa analysis demonstrated a value of 0.89 for radiographic interpretation indicating excellent agreement. Kappa values describing agreement for image interpretation for fluoroscopic imaging and CT scan were equal to 1.0, representing perfect agreement. CONCLUSIONS: Three-dimensional fluoroscopic imaging provides comparable diagnostic imaging with CT scan in an experimental cadaveric model of spondylolysis using up to 85% less radiation than conventional CT scan.

Preoperative templating before spinal fusion using a fluoroscopic multiplanar imaging system is as accurate as CT scan and uses substantially less radiation.

BACKGROUND: Many surgeons utilize preoperative multiplanar imaging for surgical planning before fusion surgery using pedicle screw instrumentation. Computed tomographic (CT) scan is often used but limited by non-weight-bearing images and high-ionizing radiation. The purpose of this study was to compare pedicle length and width measurements using a multiplanar fluoroscopic imaging system and CT with gross measurements to validate the accuracy of multiplanar fluoroscopic imaging and compare relative radiation exposure between techniques. METHODS: Thirteen intact cadaveric lumbar spine segments were imaged using multiplanar fluoroscopic imaging and conventional CT scan using a low-dose pediatric protocol. At each level and each imaging modality, the 26 pedicles were measured digitally for width and pedicle screw length in accordance with typical presurgical planning procedures. All images were independently measured by 3 observers. After measurement, the specimens were sectioned using a microsurgical saw to facilitate anatomic measurements using calipers. Measurements of the multiplanar fluoroscopic imaging and CT were compared with direct anatomic measurements to quantitate and compare measurement accuracy of CT and fluoroscopic imaging. At the time of image acquisition, radiation exposure from each modality was quantified to allow for comparison of radiation exposures. RESULTS: CT and multiplanar fluoroscopy had similar agreement with gross measurements with respect to pedicle width and length, with κ values for comparison of CT and fluoroscopy with gross measurements falling between 0.61 and 0.73. Both modalities underestimated pedicle width (by 1.9 mm for both modalities) and length (5.5 mm for CT, 6.6 mm for fluoroscopy). Interobserver reliability was higher for fluoroscopy versus CT. High-dose fluoroscopic imaging used 31% of the radiation exposure for CT. CONCLUSIONS: Multiplanar fluoroscopic imaging provides comparable diagnostic preoperative planning to CT scan in an experimental cadaveric model. The use of multiplanar fluoroscopic imaging resulted in between 69% and 85% less radiation exposure than conventional CT scan using pediatric settings. CLINICAL EVIDENCE: This study demonstrates similar results from simulated preoperative templating using fluoroscopic imaging compared with CT scan but with less radiation exposure.

Lumbar spine intervertebral disc gene delivery of BMPs induces anterior spine fusion in lewis rats.

Minimally invasive techniques and biological autograft alternatives such as the bone morphogenetic proteins (BMPs) can reduce morbidity associated with spinal fusions. This study was a proof-of-concept for gene-therapy-mediated anterior spine fusion that could be adapted to percutaneous technique for clinical use. Isogeneic bone marrow stromal cells genetically programmed to express b-galactosidase (LACZ, a marker gene), BMP2, BMP7, a mixture of BMP2 and BMP7 infected cells (homodimers, HM), or BMP2/7 heterodimers (HT) were implanted into the discs between lumbar vertebrae 4 and 5 (L4/5) and L5/6 of male Lewis rats. Spine stiffening was monitored at 4, 8 and 12 weeks using noninvasive-induced angular displacement (NIAD) testing. At 12 weeks isolated spines were assessed for fusion and bone formation by palpation, biomechanical testing [four-point bending stiffness, moment to failure in extension, and in vitro angular displacement (IVAD)], faxitron x-rays, microCT, and histology. Progressive loss of NIAD occurred in only the HT group (p < 0.001), and biomechanical tests correlated with the NIAD results. Significant fusion occurred only in the HT group (94% of animals with one or both levels) as assessed by palpation (p < 0.001), which predicted HT bone production assessed by faxitron (p ≤ 0.001) or microCT (p < 0.023). Intervertebral bridging bone was consistently observed only in HT-treated specimens. Induced bone was located anterior and lateral to the disc space, with no bone formation noted within the disc. Percutaneous anterior spine fusions may be possible clinically, but induction of bone inside the disc space remains a challenge.

Surgical treatment for atlantooccipital osteoarthritis: a case report of two patients.

BACKGROUND/PURPOSE: Although rarely discussed in the literature and difficult to evaluate on plain radiographs, atlantooccipital osteoarthritis can be a source of persistent suboccipital pain. Our objective in this report is to describe two cases with atlantooccipital (O-C1) osteoarthritis treated with posterior occipitocervical fusion. METHODS AND RESULTS: Two patients presented with unilateral suboccipital pain, which was refractory to conservative treatment. One patient suffered from long-standing rheumatoid arthritis while the other patient did not have pertinent medical issues. After non-diagnostic plain film imaging, CT scan demonstrated unilateral osteoarthritis of the atlantooccipital and atlantoaxial joint in both patients who subsequently underwent posterior O-C2 fusion with resolution of their preoperative symptoms. CONCLUSIONS: This is, to our knowledge, the first case report which specifically focused on surgical treatment of atlantooccipital osteoarthritis. Occipitocervical fusion is a treatment option for patients with atlantooccipital osteoarthritis when suboccipital pain is not responsive to conservative treatment.

Mesh cage reconstruction with autologous cancellous graft in anterior cervical discectomy and fusion.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To present the technique and results of anterior cervical discectomy and fusion (ACDF) by using mesh cage reconstruction with autologous cancellous bone graft. BACKGROUND: Since the initial ACDF description by Bailey and Badgley, a variety of grafting techniques have been proposed. The primary disadvantage of autologous bone grafting is donor site pain when compared with allograft. However, autologous bone graft still remains the standard and cancellous bone retrieval through a cortical window minimizes subperiosteal stripping. This may improve donor site morbidity while providing the advantages of autologous bone graft. METHODS: Thirty-seven patients who had undergone ACDF with cancellous bone graft by using mesh cages and anterior plating with at least 6 months follow-up were reviewed. All patients had autologous cancellous bone graft harvested through a cortical window with limited subperiosteal striping. Bone graft was then packed into and around a titanium mesh cage that furnishes structural support. RESULTS: The principal diagnosis was radiculopathy in 30 patients, myeloradiculopathy in 2 patients, instability in 3 patients, and kyphosis in 2 patients. Sixty-four levels were fused: one 4-level fusion, eight 3-level fusions, eight 2-level fusions, and twenty 1-level fusions. All patients demonstrated improved neurologic function and resolution of preoperative pain postoperatively. The donor site for cancellous bone was the iliac crest in 33 patients and the manubrium in 4 patients. Perioperative donor site pain was absent in 35 of 38 patients by 6 weeks with resolution of donor site pain by 3 months in all patients. At most recent follow-up, no patients had donor site pain, no instrumentation failure, and no wound complications. Sixty-three of 64 (98.4%) of cervical segments fused. One pseudoarthrosis occurred in an attempted 4-level fusion, which fused after a second operation. CONCLUSIONS: Autologous bone grafting with mesh cage reconstruction is an acceptable alternative to autologous tricortical structural graft or allograft with reduced donor site pain and excellent biologic arthrodesis.

Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro.

Bone morphogenic proteins (BMPs) are growth factors important for skeletal development and bone growth. Noggin, one of the soluble BMP antagonists, regulates the action of BMPs on mesenchymal precursor cells, partially through a feedback type of inhibition. In this study, we constructed a novel BMP2/7 'fusion gene' that encodes both BMP2 and BMP7 genes in tandem by a linker. Polymerase chain reaction (PCR) and Western blotting showed that the BMP2/7 fusion gene construct led to the production of BMP2/7 heterodimers in A549 'producer' cells. When applied to C2C12 myoblastic cells, BMP2/7 heterodimers increased alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression (markers of osteoblastic differentiation) more effectively than either BMP2 or BMP7 homodimers. Moreover, this heterodimer induced significantly lower levels of Noggin expression in C2C12 cells than respective homodimers at similar doses. The addition of Noggin did not affect the heterodimer's activities in increasing osteoblastic differentiation in C2C12 cells. In contrast, BMP2 and BMP7 homodimers were largely inhibited by Noggin. Our finding suggests that the 'fusion gene' construct led to the production of bioactive BMP2/7 heterodimers, which were not antagonized by Noggin as effectively as it to BMP homodimers. The weaker Noggin antagonism on BMP heterodimers compared to homodimers may contribute to increased osteogenic potency of heterodimers in vitro and in vivo.

Unplanned Reoperations Affect Long-Term Outcomes in Adult Spinal Deformity Patients Undergoing Long Fusions to the Sacrum.

STUDY DESIGN: Retrospective clinical cohort study. OBJECTIVE: To compare the long-term complications and outcomes scores of primary and revision surgeries for adult spinal deformity of patients treated with long fusions to the sacrum. SUMMARY OF BACKGROUND DATA: Long fusions in patients with adult spinal deformity are fraught with complications and the need for reoperation that can significantly impact patient health-related quality of life. METHODS: Data from 134 consecutive patients who underwent spinal fusion from the thoracic spine to the sacropelvis and had a minimum of 5-year follow-up were analyzed. Patients were classified as primary surgery (PS) and index revision (IR) surgery; they were then subdivided based on whether they returned to the operating room (RTO) or not (NRTO). RTO complications were classified as 1) infection, 2) neurologic, 3) fusion status, 4) implants, and 5) global alignment and stratified as <6 months, <2 years, and >2 years. Final Scoliosis Research Society Patient Questionnaire (SRS 22r) and Oswestry Disability Index (ODI) scores were compared between subgroups. RESULTS: Seventy-one PS and 63 IR were included in the analysis. Mean age at surgery was 54.9 years (30-78), mean follow-up 5.8 years (4.9-12.8). RTO rates were 21.1% and 34.9%, respectively, for PS and IR (p = .16). 43.8% of patients requiring reoperation did so on multiple occasions. Fifty PS and 41 IR cases had complete SRS 22 and ODI scores. Final SRS 22 total scores were 3.74 and 3.41 (p = .02) for the respective groups. ODI scores were 25.4% and 34.0% (p = .02). CONCLUSIONS: Both groups had a significant number of revision surgeries performed by 5 years of follow-up. Unplanned reoperation significantly affected ODI and SRS 22 outcomes scores in the individual domains of pain, function, and overall satisfaction as well as total score at the 5-year follow-up regardless of PS or IR status. Overall, the PS group had improved outcomes when compared to the IR group.

Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model.

UNLABELLED: To enhance the osteogenic activity of BMP, combination BMP2 and BMP7 gene transfer was performed. This approach led to a significant increase in osteoblastic differentiation of mesenchymal precursors compared with single BMP gene transfer in vitro. When tested in 78 rats, combination gene transfer enhanced mechanically stable spine fusion and bone formation rate versus single BMP gene transfer. INTRODUCTION: Although clinical bone morphogenetic protein (BMP) therapy is effective, required doses are very high. Previous studies have suggested that the co-expression of two different BMP genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP2 and BMP7 gene transfer was performed to test whether this approach improves osteoblastic differentiation and bone formation compared with single BMP gene transfer. MATERIALS AND METHODS: A producer cell (A549) was co-transfected with adenovirus vectors encoding BMP2 (AdBMP2) and BMP7 (AdBMP7) or, as controls, each vector alone, AdNull (with no transgene) or no virus. Supernatants were compared for their ability to stimulate osteoblastic differentiation of C2C12 myoblasts and MC3T3-E1 pre-osteoblasts. In a rat posterolateral spine fusion model, co-administration of AdBMP2 and AdBMP7 was compared with treatment with each vector alone, AdNull or no virus in 78 rats. The spines were assessed 8 weeks after surgery for radiographic and mechanical fusion, bone formation, and mineralization. RESULTS: BMP2 and BMP7 were co-precipitated from supernatants of cells co-transfected with AdBMP2 and AdBMP7, indicating the presence of BMP2/7 heterodimer. Supernatants of co-transfected cells containing relatively low doses (7-140 ng/ml) of BMPs induced osteocalcin expression and alkaline phosphatase activity in both C2C12 and MC3T3-E1 cells, that were up to 6- and 40-fold higher, respectively, than levels induced by maximal doses (200-1000 ng/ml) of either BMP2 or BMP7 alone. In the spine fusion model, co-administration of AdBMP2 and AdBMP7 resulted in a significantly greater number of mechanically stable fusions and also 2-fold higher mineralization rate and bone volume in the fusion mass versus single BMP gene transfer (p < 0.02, all comparisons). CONCLUSION: Combined BMP2 and BMP7 gene transfer is significantly more effective in inducing osteoblastic differentiation and spine fusion than individual BMP gene transfer.

Lumbar spine intervertebral disc gene delivery: a pilot study in lewis rats.

BACKGROUND: Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc. PURPOSE: This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery. METHODS: Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure. RESULTS: Statistically significant differences were noted for recovery of the ß-galactosidase marker gene comparing delivery of naïve or labeled cells (10(5) cells per disc) from the site of implantation, and between delivery of 10(5) or 10(6) labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the ß-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation. CONCLUSIONS: The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.

The effect of sacral decortication on lumbosacral fixation in a calf spine model.

STUDY DESIGN: Animal cadaveric biomechanical study. OBJECTIVE: We hypothesized that increasing bony destabilization of a bovine cadaveric sacrum by anterior pedicle screw penetration and bilateral alar decortication would decrease the amount of load necessary for failure of the construct and result in failure through the decortication sites. SUMMARY OF BACKGROUND DATA: Fusion to the sacrum has become commonly used for treatment of neuromuscular scoliosis and fusions in osteoporotic patients. Fixation failure after attempted fusion to the sacrum may be attributed to iatrogenic causes such as S1 screw penetration and sacral ala decortication. METHODS: Sixteen fresh-frozen 6- to 8-week-old calf spines were tested after instrumentation with pedicle screws and bilateral rods from L2 to S1 using four constructs: (1) S1 screws with posterior-only purchase; (2) S1 screws with bicortical purchase; (3) S1 screws with bicortical purchase and sacral alar decortication; and (4) S1 screws with bicortical purchase, decortication, and iliac fixation. A destructive flexural bending load was applied at L2 to each construct. Ultimate failure moment (Nm) was compared among the four groups, using a one-way analysis of variance combined with Holm-Sidak post hoc test. RESULTS: No significant difference in failure moment was found among groups 1, 2, and 3. The addition of iliac fixation (group 4) significantly increased bending load to failure (P < 0.01), and iliac screw dislodgement was the dominant mechanism of failure. All specimens in group 3 failed with fractures extending through the decortication site. Groups 1 and 2 specimens failed by fracturing through the S1 body. CONCLUSION: Sacral alar decortication and anterior pedicle screw purchase did not decrease the failure moment in long instrumentation to the sacrum. Pattern of failure was affected, with alar decortication being the site of fracture in each construct in which it was performed. Iliac fixation increased the failure moment under catastrophic loading conditions even when combined with sacral alar decortication and bicortical pedicle screw purchase.

Long-term magnetic resonance imaging follow-up demonstrates minimal transitional level lumbar disc degeneration after posterior spine fusion for adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To describe long-term clinical and imaging results focusing on the uninstrumented lumbar spine after posterior spinal fusion for adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Although previous studies found rates of low back pain after long fusion for adolescent idiopathic scoliosis which are comparable to rates found in the general population, many surgeons believe that the long lever arm associated with the fusion mass will result in increased stress at uninstrumented caudal intervertebral discs and accelerated degenerative changes. METHODS: This is a retrospective chart and imaging review of adolescent idiopathic scoliosis patients treated with posterior fusion and segmental instrumentation. Patients completed follow-up examination, outcome questionnaires, radiographs, and magnetic resonance (MR) imaging. MR images were scored for evidence of degeneration of lumbar discs below the level of the fusion. RESULTS: Twenty patients participated in the study, providing 90 discs below fusions for evaluation. The average follow-up was 11.8 years. The distal level of fixation was at L1 on average. The major curve averaged 55° ± 11° before surgery and was corrected to 25° ± 10° at follow-up. Follow-up MR imaging demonstrated new disc pathology in 85% of patients enrolled. Only one patient demonstrated significant degenerative disc disease at the junctional level, whereas most pathology was seen at the L5-S1 disc. The average Pfirrmann grade at uninstrumented levels deteriorated from 1.1 before surgery to 1.8 at follow-up. The greatest degree of degeneration was seen at the L5-S1 disc space where average degenerative scores increased from 1.2 before surgery to 2.3 after surgery. Three patients with severe disc disease were taking nonsteroidal anti-inflammatory drugs for pain, but no narcotics. Only mild scoliosis research society (SRS) and Oswestry changes were noted in this severe degeneration group. CONCLUSION: Despite demonstrating an accelerated rate of L5-S1 disc degeneration, our study group has good functional scores and maintenance of correction over 10 years postfusion. In this long-term MR imaging follow-up study, disc degeneration was found remote to the lowest instrumented vertebra.

Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells.

Stromal derived factor-1 (SDF-1) is a chemokine signaling molecule that binds to its transmembrane receptor CXC chemokine receptor-4 (CXCR4). While we previously detected that SDF-1 was co-required with bone morphogenetic protein 2 (BMP2) for differentiating mesenchymal C2C12 cells into osteoblastic cells, it is unknown whether SDF-1 is similarly involved in the osteogenic differentiation of mesenchymal stem cells (MSCs). Therefore, here we examined the role of SDF-1 signaling during BMP2-induced osteogenic differentiation of primary MSCs that were derived from human and mouse bone marrow. Our data showed that blocking of the SDF-1/CXCR4 signal axis or adding SDF-1 protein to MSCs significantly affected BMP2-induced alkaline phosphatase (ALP) activity and osteocalcin (OCN) synthesis, markers of preosteoblasts and mature osteoblasts, respectively. Moreover, disrupting the SDF-1 signaling impaired bone nodule mineralization during terminal differentiation of MSCs. Furthermore, we detected that blocking of the SDF-1 signaling inhibited the BMP2-induced early expression of Runt-related factor-2 (Runx2) and osterix (Osx), two "master" regulators of osteogenesis, and the SDF-1 effect was mediated via intracellular Smad and Erk activation. In conclusion, our results demonstrated a regulatory role of SDF-1 in BMP2-induced osteogenic differentiation of MSCs, as perturbing the SDF-1 signaling affected the differentiation of MSCs towards osteoblastic cells in response to BMP2 stimulation. These data provide novel insights into molecular mechanisms underlying MSC osteogenesis, and will contribute to the development of MSC therapies for enhancing bone formation and regeneration in broad orthopaedic situations.

Thromboembolic disease after combined anterior/posterior reconstruction for adult spinal deformity: a prospective cohort study using magnetic resonance venography.

STUDY DESIGN: Thromboembolic disease (TED) after anterior/posterior spinal reconstructions was prospectively evaluated in 66 consecutive patients. OBJECTIVE: Determine the incidence of TED after anterior/posterior spinal reconstruction. SUMMARY OF BACKGROUND DATA: Few studies have examined the rate of TED after potentially high-risk combined anterior/posterior reconstructions. Magnetic resonance venography (MRV) is more effective at detecting pelvic deep venous thrombosis (DVT) than conventional screening, but has not been used in these patients. METHODS: We undertook a prospective cohort study of 66 consecutive adult patients (mean, 52.7 +/- 9.6 years) undergoing combined anterior/posterior spinal reconstructions for spinal deformity. All patients received only mechanical DVT prophylaxis. After surgery, MRV and bilateral lower extremity Doppler ultrasounds were obtained to screen for DVT, and contrast-enhanced spiral computed tomography scans were obtained for clinical suspicion of pulmonary embolism (PE). RESULTS: The total incidence of postoperative TED was 13.6% (9 patients). The overall rate of DVT was 9.1% (6 patients), one-third occurring in the pelvis. PE developed in 7.6% (5 patients). In 2 patients, PE developed less than 48 hours after positive dopplers. In 3 patients, PE developed despite negative screening studies. Right-sided thoracoabdominal approaches were associated with an increased risk of developing DVT (P = 0.03, Odds Ratio 9.8), PE (P = 0.01, Odds Ratio 20), and TED (P = 0.004, Odds Ratio 12). CONCLUSION: We report a high rate of TED after extensive anterior/posterior spinal reconstructions, for which a right-sided thoracoabdominal approach is an independent risk factor and screening ineffective at preventing PE. These patients should be considered at high risk for postoperative TED.

A novel source of cancellous autograft for ACDF surgery: the manubrium.

There are a variety of techniques and biologic options when performing interbody fusion during an anterior cervical discectomy and fusion (ACDF). Autologous graft provides high rates of fusion; however, complications associated with donor site morbidity from the iliac crest have prompted some surgeons to use alternative graft material. Ten patients (8 men, 2 women) with cervical radiculopathy underwent single-level ACDF with plate fixation, titanium mesh cage, and cancellous autograft from the manubrium. Cancellous bone was obtained through a cortical window on the anterior aspect of the manubrium through a 2-cm transverse incision. A minimum 1-year clinical and radiographic follow-up for all patients evaluated fusion rates, donor site morbidity, and patient satisfaction. All patients had immediate postoperative resolution of radicular symptoms and radiographic evidence of solid fusion within 3 months. No patient complained of donor site pain and narcotic pain medication was not required after discharge. No complications associated with the manubrium donor site were noted; however, 1 female patient was dissatisfied with its cosmetic appearance. The manubrium is an effective, safe, and technically facile source of autologous bone graft that yields high fusion rates and patient satisfaction in contemporary ACDF surgery. This new technique to obtain cancellous graft from the manubrium combines the advantages of autologous bone without the morbidity of iliac crest harvest.

A novel regulatory role for stromal-derived factor-1 signaling in bone morphogenic protein-2 osteogenic differentiation of mesenchymal C2C12 cells.

Stromal-derived factor 1 (SDF-1) is a chemokine with important functions in development and postnatal tissue homeostasis. SDF-1 signaling via the G-protein-coupled receptor CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study we examined the contribution of SDF-1 signaling to osteogenic differentiation of mesenchymal C2C12 cells induced by bone morphogenic protein 2 (BMP2). Blocking SDF-1 signaling before BMP2 stimulation by treatment with siRNA, antibodies against SDF-1 or CXCR4, or the G-protein-coupled receptor inhibitor pertussis toxin strongly suppressed BMP2 induction of osteogenic differentiation in C2C12 cells, as evidenced by an early decrease in the expression of the myogenesis inhibitor Id1, the osteogenic master regulators Runx2 and Osx, the osteoblast-associated transcription factors JunB, Plzf, Msx2, and Dlx5, and later of the bone marker proteins osteocalcin and alkaline phosphatase. Similarly, blocking SDF-1/CXCR4 signaling strongly inhibited BMP2-induced osteogenic differentiation of ST2 bone marrow stromal cells. Moreover, we found that the interaction between SDF-1 and BMP2 signaling was mediated via intracellular Smads and MAPK activation. Our data provide the first evidence for a co-requirement of the SDF-1/CXCR4 signaling axis in BMP2-induced osteogenic differentiation of C2C12 and ST2 cells and, thus, uncover a new potential target for modulation of osteogenesis.

Comprehensive analysis of cantilever, translational, and modular corrective techniques in adults with scoliosis treated with surgery to the sacropelvis.

BACKGROUND: The treatment of adults with scoliosis has been the source of debate over the last several decades. Pain associated with curve progression and decompensation is the most common presenting scenario and surgical management is often indicated. Correction of these deformities may involve long segment fusions to the sacrum and pelvis. Most authors have reported high rates of complications associated with this procedure. There remains little consensus with regard to the treatment of this challenging condition. PURPOSE: The purpose of this study was to evaluate the clinical and radiographic outcomes of patients treated with long fusions to the sacrum and pelvis using third generation instrumentation techniques. These included the use of cantilever, translational, and modular corrective techniques. METHODS: Inpatient and outpatient charts were reviewed for 97 patients (89 women and 8 men). The average age was 55 years (27 to 78 y). The information obtained included patient age, sex, comorbidities, perioperative complications, and long-term clinical outcome. Standing radiographic coronal and sagittal measurements were recorded preoperatively, immediately postoperatively, and at the most recent follow-up visit. RESULTS: Eighty-nine patients underwent combined anterior and posterior surgery, whereas 8 patients were treated with posterior-only procedures. Two patients had fixation to the sacrum without extension into the ilium. Structural curves averaged 53 degrees preoperatively, 32 degrees postoperatively, and 33 degrees at follow-up. Thoracic kyphosis averaged +36 degrees preoperatively, +39 degrees postoperatively, and +46 degrees at follow-up. Lumbar lordosis averaged -41 degrees preoperatively, -48 degrees postoperatively, and -48 degrees at follow-up. Coronal imbalance averaged 2.9 cm preoperatively, 2.4 cm postoperatively, and 2.3 cm at follow-up. Sagittal imbalance averaged 6.8 cm preoperatively, 2.9 cm postoperatively, and 3.6 cm at follow-up. Major complications included pseudarthrosis (10%), deep infection (13%), painful iliac fixation (20%), neurologic injury (6%), need for some form of revision surgery (39%), chronic severe pain (2%), pulmonary embolism (2%), and deep venous thrombosis (2%). There were no permanent neurologic injuries or deaths related to the surgery.

The treatment of large (>70 degrees) thoracic idiopathic scoliosis curves with posterior instrumentation and arthrodesis: when is anterior release indicated?

STUDY DESIGN: Retrospective clinical study from 2 centers. OBJECTIVE: To analyze the efficacy of posterior instrumentation and arthrodesis for thoracic idiopathic scoliosis curves more than 70 degrees. SUMMARY OF BACKGROUND INFORMATION: The increasing use of thoracoscopic techniques in deformity surgery has led several investigators to advocate anterior release followed by posterior instrumentation when treating "stiff" thoracic curves 60 degrees-70 degrees. To our knowledge, no study has been published to define indications for anterior surgery in thoracic idiopathic scoliosis. METHODS: This is a retrospective review of patients 20 years and younger, with idiopathic scoliosis and thoracic curves more than 70 degrees treated with isolated posterior instrumentation and arthrodesis at 2 institutions from 1989 to 1999. A total of 50 patients were identified, and 46 were available for minimum 2-year radiographic follow-up. Of the 50 patients, 44 had bend films taken before surgery. All patients were treated with third-generation segmental spinal instrumentation using a varied combination of hooks, wires, and screws. RESULTS: Average patient age at surgery was 14.4 years (range 10-20), and average radiographic follow-up was 4.4 years (range 2-11.5). Average preoperative thoracic curve was 75 degrees (range 70 degrees-88 degrees), and average bend was 47 degrees (range 28 degrees-60 degrees), a flexibility of 37%. Average postoperative curve was 25 degrees (range 10 degrees-46 degrees), and it was 27 degrees (range 11 degrees-46 degrees) at latest follow-up, a correction of 64%. The average length of surgery was 6.15 hours, mean hospital stay was 8 days, and average blood loss was 1100 cc. The Scoliosis Research Society 22 or 24 was available at a minimum of 2 years in 46 of 50 patients. Mean domain scores were: pain 4.4, self-image 4.3, function 4.3, mental health 4.3, satisfaction 4.7, and total 4.4. Complications included 1 pseudarthrosis, 1 implant removal for prominence, and 1 implant removal for late operative site pain. CONCLUSION: Using posterior surgery only, we have been able to at least equal the results reported in the literature by investigators using combined approaches. Isolated posterior instrumentation and arthrodesis achieve satisfactory cosmetic, radiographic, and patient-based outcomes in adolescents with idiopathic scoliosis with thoracic curves 70 degrees-90 degrees, without the added expense and morbidity of anterior release.

Not all spondylolisthesis grading instruments are reliable.

Spondylolisthesis is the slippage of one vertebral body on an adjacent level, and occurs commonly at the lumbosacral junction in children. Many radiographic measurement instruments have been described to predict progression and need for intervention. We evaluated the reliability of eight common grading instruments. Four raters reviewed 30 lateral radiographs of the lumbar spine in patients with spondylolisthesis. Each rater measured each film twice, and had mean individual correlation coefficients of at least 0.76 (range, 0.76-0.91). Only three measurements had interobserver correlations greater than 0.75 (slip percentage, Meyerding's grade, and sacral inclination), which corresponded to excellent reliability. For intraobserver reliability, six measurements had correlations greater than 0.75 (all except kyphosis angle and lumbar index), indicating excellent agreement. Slip percent, Meyerding's grade, and sacral inclination had excellent interobserver agreement and intraobserver agreement.