Secreted phosphoprotein 24 kD (Spp24) inhibits the growth of human osteosarcoma through the BMP-2/Smad signaling pathway.

Autocrine stimulation of tumor cells is an important mechanism for the growth of skeletal tumors. In tumors that are sensitive, growth factor inhibitors can dramatically reduce tumor growth. In this study, our aim was to investigate the effects of Secreted phosphoprotein 24 kD (Spp24) on the growth of osteosarcoma (OS) cells in the presence and absence of exogenous BMP-2 both in vitro and in vivo. Our study demonstrated that Spp24 inhibited proliferation and promoted apoptosis of OS cells as confirmed by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay and immunohistochemical staining. We found that BMP-2 increased the mobility and invasiveness of tumor cells in vitro whereas Spp24 inhibited both of these processes alone and in the presence of exogenous BMP-2. Phosphorylation of Smad1/5/8 and Smad8 gene expression was enhanced by treatment with BMP-2 but inhibited by treatment with Spp24. Subcutaneous and intratibial tumor models in nude mice demonstrated that BMP-2 promoted OS growth in vivo, while Spp24 significantly inhibited tumor growth. We conclude that the BMP-2/Smad signaling pathway is involved in the pathogenesis of OS growth and that Spp24 inhibits the growth of human OS induced by BMP-2 both in vitro and in vivo. Interruption of Smad signaling and increased apoptosis appear to be the primary mechanisms involved. These results confirm the potential of Spp24 as a therapeutic agent for the treatment of OS and other skeletal tumors.

Patterns of Lumbar Disc Degeneration: Magnetic Resonance Imaging Analysis in Symptomatic Subjects.

STUDY DESIGN: Cross-sectional study. PURPOSE: To evaluate lumbar disc degeneration (LDD) on magnetic resonance imaging (MRI) in symptomatic subjects to accumulate baseline data on the pattern of degeneration. OVERVIEW OF LITERATURE: LDD plays an important role in the diagnosis and treatment of low-back pain in patients. Few studies have focused on the pattern of LDD to understand how the lumbar spine ages. METHODS: This study included 1,095 patients (mean age, 44.29 years; range, 16-85 years) who underwent upright lumbar MRI. LDD was graded into five categories (I-V). Positive LDD was defined as grade III or greater. The prevalence and pattern of LDD were analyzed, and the correlations between age and total grade of LDD were evaluated. RESULTS: The average number of LDD levels and the total grade of LDD increased with age. LDD moved cephalad with age. The rate of LDD increased rapidly during the decade before the prevalence of LDD and became >50%. In the single-level LDD group, the levels L5-S1 were the most common levels (60.3%). In the two-level group, L4-L5 and L5-S1 were the most common levels (53.5%). In the three-level group, L3-L4, L4-L5, and L5-S1 were the most common levels (55.7%). In the multilevel LDD group, contiguous multilevel disc degeneration (CMDD) was more common than the skipped level disc degeneration (SLDD). The levels L4-L5 were the most common levels in the CMDD group, and L5-S1 were the most common levels among SLDD. CONCLUSIONS: LDD was found to correlate with age, and the specific patterns and rates of LDD depended on lumbar disc level and age. These LDD pattern data can be used before spinal procedures to predict the probability of natural LDD progression with age.

Preoperative Maximization to Reduce Complications in Spinal Surgery.

STUDY DESIGN: Invited narrative review. OBJECTIVES: The aim of this review was to summarize current literature regarding risk factors that surgeons can optimize in the preoperative setting in the spinal surgery patient, in order to reduce complications and improve patient-reported outcomes. METHODS: Review of the relevant literature by the authors. RESULTS: Modifiable risk factors identified relative to the patient include obesity, malnutrition/nutrient deficiency, diabetes/hyperglycemia, preoperative anemia, vitamin D/DEXA (dual-energy radiograph absorptiometry), nicotine use/smoking, and opioid use/psychosocial factors. CONCLUSION: By maximizing a patient's physiological and psychological status prior to elective spine surgery, we may move closer to achieving the goals of value-based care: improving patient-reported outcomes while decreasing the cost of care.

Minimizing Blood Loss in Spine Surgery.

STUDY DESIGN: Broad narrative review. OBJECTIVE: To review and summarize the current literature on guidelines, outcomes, techniques and indications surrounding multiple modalities of minimizing blood loss in spine surgery. METHODS: A thorough review of peer-reviewed literature was performed on the guidelines, outcomes, techniques, and indications for multiple modalities of minimizing blood loss in spine surgery. RESULTS: There is a large body of literature that provides a consensus on guidelines regarding the appropriate timing of discontinuation of anticoagulation, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and herbal supplements prior to surgery. Additionally, there is a more heterogenous discussion the utility of preoperative autologous blood donation facilitated by erythropoietin and iron supplementation for healthy patients slated for procedures with high anticipated blood loss and for whom allogeneic transfusion is likely. Intraoperative maneuvers available to minimize blood loss include positioning and maintaining normothermia. Tranexamic acid (TXA), bipolar sealer electrocautery, and topical hemostatic agents, and hypotensive anesthesia (mean arterial pressure (MAP) <65 mm Hg) should be strongly considered in cases with larger exposures and higher anticipated blood loss. There is strong level 1 evidence for the use of TXA in spine surgery as it reduces the overall blood loss and transfusion requirements. CONCLUSION: As the volume and complexity of spinal procedures rise, intraoperative blood loss management has become a pivotal topic of research within the field. There are many tools for minimizing blood loss in patients undergoing spine surgery. The current literature supports combining techniques to use a cost- effective multimodal approach to minimize blood loss in the perioperative period.

Bone morphogenetic protein-2 promotes osteosarcoma growth by promoting epithelial-mesenchymal transition (EMT) through the Wnt/ß-catenin signaling pathway.

The correlation between BMP-2 and osteosarcoma growth has gained increased interest in the recent years, however, there is still no consensus. In this study, we tested the effects of BMP-2 on osteosarcoma cells through both in vitro and in vivo experiments. The effect of BMP-2 on the proliferation, migration and invasion of osteosarcoma cells was tested in vitro. Subcutaneous and intratibial tumor models were used for the in vivo experiments in nude mice. The effects of BMP-2 on EMT of osteosarcoma cells and the Wnt/ß-catenin signaling pathway were also tested using a variety of biochemical methods. In vitro tests did not show a significant effect of BMP-2 on tumor cell proliferation. However, BMP-2 increased the mobility of tumor cells and the invasion assay demonstrated that BMP-2 promoted invasion of osteosarcoma cells in vitro. In vivo animal study showed that BMP-2 dramatically enhanced tumor growth. We also found that BMP-2 induced EMT of osteosarcoma cells. The expression levels of Axin2 and Dkk-1 were both down regulated by BMP-2 treatment, while ß-catenin, c-myc and Cyclin-D1 were all upregulated. The expression of Wnt3α and p-GSK-3ß were also significantly upregulated indicating that the Wnt/ß-catenin signaling pathway was activated during the EMT of osteosarcoma driven by BMP-2. From this study, we can conclude that BMP-2 significantly promotes growth of osteosarcoma cells (143B, MG63), and enhances mobility and invasiveness of tumor cells as demonstrated in vitro. The underlying mechanism might be that BMP-2 promotes EMT of osteosarcoma through the Wnt/ß-catenin signaling pathway. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1638-1648, 2019.

Patterns of Cervical Disc Degeneration: Analysis of Magnetic Resonance Imaging of Over 1000 Symptomatic Subjects.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: The aim of this study was to evaluate cervical disc degeneration on magnetic resonance imaging (MRI) in a large population of symptomatic patients and to provide baseline data on the pattern of degeneration in order to understand how the cervical spine ages. METHODS: We performed a cross-sectional study of 1059 patients who underwent upright cervical MRI for neck pain with and without neurological symptoms. A total of 6354 cervical discs from C2/3 to C7/T1 were evaluated. Cervical disc degeneration was evaluated on T2-weighted MRI and graded into 4 categories (Grades 0-III). Positive degeneration was defined as greater than Grade II. The correlation between age and total grade of degeneration of each patient was evaluated, as well as the prevalence and pattern of degeneration. RESULTS: The average number of degenerated disc levels and the total grade of cervical disc degeneration significantly increase with age. In the patient group with 1-level degeneration, C5/6 was the most common degenerated level followed by C4/5 and C6/7. In the group with 2-level degeneration, C5/6 & C6/7 was most common followed by C4/5 & C5/6 and C3/4 & C4/5. Skip level degeneration was significantly rarer than contiguous level degeneration, and C7/T1 and C2/3 were the most unlikely to degenerate in multilevel degeneration. CONCLUSION: Disc degeneration is most common in the middle cervical spine (C5/6) and progresses to contiguous levels, except for C7/T1 and C2/3. This pattern may play a role in adjacent-level disc degeneration associated with spinal fusion.

How does sagittal imbalance affect the appropriateness of surgical indications and selection of procedure in the treatment of degenerative scoliosis? Findings from the RAND/UCLA Appropriate Use Criteria study.

BACKGROUND CONTEXT: Degenerative lumbar scoliosis (DLS) is often associated with sagittal imbalance, which may affect patients' health outcomes before and after surgery. The appropriateness of surgery and preferred operative approaches has not been examined in detail for patients with DLS and sagittal imbalance. PURPOSE: The goals of this article were to describe what is currently known about the relationship between sagittal imbalance and health outcomes among patients with DLS and to determine how indications for surgery in patients with DLS differ when sagittal imbalance is present. STUDY DESIGN/SETTING: This study included a literature review and an expert panel using the RAND/University of California at Los Angeles (UCLA) Appropriateness Method. METHODS: To develop appropriate use criteria for DLS, researchers at the RAND Corporation recently employed the RAND/UCLA Appropriateness Method, which involves a systematic review of the literature and multidisciplinary expert panel process. Experts reviewed a synopsis of published literature and rated the appropriateness of five common operative approaches for 260 different clinical scenarios. In the present work, we updated the literature review and compared panelists' ratings in scenarios where imbalance was present versus absent. This work was funded by the Collaborative Spine Research Foundation, a group of surgical specialty societies and device manufacturers. RESULTS: On the basis of 13 eligible studies that examined sagittal imbalance and outcomes in patients with DLS, imbalance was associated with worse functional status in the absence of surgery and worse symptoms and complications postoperatively. Panelists' ratings demonstrated a consistent pattern across the diverse clinical scenarios. In general, when imbalance was present, surgery was more likely to be appropriate or necessary, including in some situations where surgery would otherwise be inappropriate. For patients with moderate to severe symptoms and imbalance, a deformity correction procedure was usually appropriate and frequently necessary, except in some patients with severe risk factors for complications. Conversely, procedures that did not correct imbalance, when present, were usually inappropriate. CONCLUSIONS: Clinical experts agreed that sagittal imbalance is a major factor affecting both when surgery is appropriate and which type of procedure is preferred among patients with DLS.

Different Fusion Approaches for Single-level Lumbar Spondylolysis Have Similar Perioperative Outcomes.

STUDY DESIGN: Retrospective cohort study OBJECTIVE.: The aim of this study was to compare perioperative adverse events for patients with lumbar spondylolysis treated with transforaminal lumbar interbody fusion (TLIF), posterior spinal fusion (PSF), combined anterior and posterior fusion (AP fusion), or anterior lumbar interbody fusion (ALIF). SUMMARY OF BACKGROUND DATA: Previous cohort studies have shown similar long-term outcomes for different surgical approaches for this indication, but potential differences in 30-day perioperative adverse events have not been well characterized. METHODS: The present study uses data extracted from the American College of Surgeons National Surgical Quality Improvement Database. Patients undergoing fusion with different approaches for lumbar spondylolysis were identified. Propensity score matching was utilized to account for potential differences in demographic and comorbidity factors. Comparisons among perioperative outcomes were then made among the propensity score-matched study groups. RESULTS: Of 1077 cases of spondylolysis identified, 556 underwent TLIF, 327 underwent PSF, 108 underwent AP fusion, and 86 underwent ALIF. After propensity score matching, there were no differences in the rates of any of the 30-day individual adverse events studied and no differences in the aggregated groupings of any adverse event, serious adverse event, or minor adverse event. There was a significantly increased operative time in the AP fusion group, but there were no differences in hospital length of stay or readmission rates. CONCLUSION: Because perioperative adverse event rates were similar, even with a slightly longer operative time in the AP fusion group, these findings suggest that surgeon preference and long-term outcomes are better used to determine the recommendation of one surgical approach over another for single level fusions for lumbar spondylolysis. LEVEL OF EVIDENCE: 3.

Results of the 2015 Scoliosis Research Society Survey on Single Versus Dual Attending Surgeon Approach for Adult Spinal Deformity Surgery.

STUDY DESIGN: An electronic survey administered to Scoliosis Research Society (SRS) membership. OBJECTIVE: To characterize surgeon practices and views regarding the use of two attending surgeons for adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: The use of two experienced attending surgeons can decrease the operative time, estimated blood loss, and perioperative complication rates. However, the current practice patterns for the use of two attending surgeons remains unknown. METHODS: An electronic, 27-question survey regarding single/dual attending surgeons was administered to the SRS membership. Determinants included: surgeon/practice demographics, assistant type/level of training, and questions regarding use of two attending surgeons. Overall reporting and comparisons between groups were made: US versus international, academic versus private practice, and experience <15 years versus >15 years. RESULTS: A total of 199 surgeons responded from 27 different countries. Overall and between the groups, the respondents significantly reported believing that two attending spine surgeons improves safety, decreases complications, and improves outcomes (P < 0.01). Approximately, 67.3% reported using a second attending ≤25% of the time (33.2% do not), and 24.1% use one ≥51% of the time (similar between groups); 51.1% that have a second attending feel it's limited by reimbursement and access concerns and 71.9% have difficulty getting the second attending reimbursed. 72.3% use a second attending for ALL of the following reasons (no difference between groups): "it's safer/reduces complications," "it decreases operative time," "it decreases blood loss," "it results in improved outcomes," "it's less work and stress for me." If reimbursement was equal/assured for a second attending, 67.5% would use one "more often" or "always." CONCLUSION: The respondents feel that having a second attending surgeon improves patient care, however most do not use one often. Reasons include reimbursement/access concerns and the majority would use one if reimbursement was equal and assured. Based on the current literature and these results, there is a need for working with third party payers to improve dual surgeon reimbursement rates in complex cases. LEVEL OF EVIDENCE: 5.

Magnetic Resonance Classification System of Cervical Intervertebral Disk Degeneration: Its Validity and Meaning.

STUDY DESIGN: Retrospective analysis of kinetic magnetic resonance images (kMRIs). OBJECTIVE: (1) To analyze the changes seen on MRI related to disk degeneration and to develop a new grading system for cervical disk degeneration. (2) To evaluate the reliability and validity of the grading system. SUMMARY OF BACKGROUND DATA: Few have studied the relationship between changes seen on MRI with cervical disk degeneration and the chronological order of disk degeneration. A few grading systems for cervical disk degeneration have been reported; however, there have been problems related to subjectivity and lack of a clear, reliable algorithm. METHODS: A total of 300 cervical intervertebral disks were graded for nucleus color, structure, disk bulge, and disk height. On the basis of the analysis, a new grading system consisting of 4 grades (grade 0-III) and algorithm were developed. Intraobserver and interobserver reliabilities were assessed. A total of 2802 intervertebral disks were then evaluated using the grading system to correlate disk degeneration grades with patient age and function and to evaluate the validity of the new system. RESULTS: On the basis of cross-table analysis, disk degeneration presents in the following order: (1) decrease and/or change of nucleus intensity; (2) loss of distinction between nucleus and annulus; (3) positive disk bulge; and (4) disk height decrease. The κ-coefficients for intraobserver and interobserver agreements were 0.96 and 0.90, respectively. Severe disk degeneration is most common at C5/C6 followed by C6/C7 and C4/C5, and total disk degeneration grade is correlated with age (R=0.467). There was a decrease of angular motion in grades I-III and an increase in translational motion and decrease of space available for the cord in grades II-III. CONCLUSIONS: We developed a new classification system of cervical disk degeneration based on analysis of the changes seen on MRI. Reliability tests indicated high reproducibility of this system, and further analysis confirmed its validity and clinical significance.

Dynamic Evaluation of the Cervical Spine and the Spinal Cord of Symptomatic Patients Using a Kinetic Magnetic Resonance Imaging Technique.

PURPOSE: The purpose of this study was to examine the movement of the spinal cord and its relationship to the spinal canal in patients with mild spondylosis using kinetic magnetic resonance imaging (kMRI). METHODS: Weight-bearing, multiposition kMRI was performed on symptomatic patients through a full range of flexion-extension. A total of 52 study patients were selected based on the C2-C7 Cobb angle of sagittal alignment: lordotic (from 30 to 45 degrees). We evaluated dynamic changes in different parameters from flexion-extension: spinal canal diameter (CD), spinal cord diameter (SCD), space available for the cord, anterior space available for the cord (ASAC), posterior space available for the cord (PSAC), average distance between the anterior canal and the cord (d-value), and global angle for the spinal canal and cord. RESULTS: The CD tended to decrease from flexion to extension from C3/C4 to C6/C7, however, there were no significant differences at the proximal and distal levels, C2/C3 and C7/T1. There were no significant differences of SCD between different postures. The SCD tended to decrease from C2/C3 to C7/T1. The ASAC followed the same pattern as CD-values. The ASAC was narrowest at C4/C5 and C5/C6. The PSAC tended to increase from C2/C3 to C7/T1. The spinal cord shifted anteriorly with extension and posteriorly with flexion. In addition, the spinal cord maintained its curve with the movement. CONCLUSIONS: The kinematics of spinal cord motion may be associated with the pathogenesis of cervical spondylotic myelopathy. However, the spinal cord maintains its curve with position changes. Consequently, different motions of the cervical spine may affect spinal cord migration and cause changes in ASAC and PSAC.

Adult Spinal Deformity: Epidemiology, Health Impact, Evaluation, and Management.

Spinal deformity in the adult is a common medical disorder with a significant and measurable impact on health-related quality of life. The ability to measure and quantify patient self-reported health status with disease-specific and general health status measures, and to correlate health status with radiographic and clinical measures of spinal deformity, has enabled significant advances in the assessment of the impact of deformity on our population, and in the evaluation and management of spinal deformity using an evidence-based approach. There has been a significant paradigm shift in the evaluation and management of patients with adult deformity. The paradigm shift includes development of validated, disease-specific measures of health status, recognition of deformity in the sagittal plane as a primary determinant of health status, and information on results of operative and medical/interventional management strategies for adults with spinal deformity. Since its inception in 1966, the Scoliosis Research Society (SRS) has been an international catalyst for improving the research and care for patients of all ages with spinal deformity. The SRS Adult Spinal Deformity Committee serves the mission of developing and defining an evidence-based approach to the evaluation and management of adult spinal deformity. The purpose of this overview from the SRS Adult Deformity Committee is to provide current information on the epidemiology and impact of adult deformity, and to provide patients, physicians, and policy makers a guide to the evidence-based evaluation and management of patients with adult deformity.

Outcomes of Demineralized Bone Matrix Enriched with Concentrated Bone Marrow Aspirate in Lumbar Fusion.

BACKGROUND: Multiple studies have demonstrated that a significant amount of variability exists in various demineralized bone matrix (DBM) formulations, which casts doubts on its reliability in consistently promoting fusion. Bone marrow aspirate (BMA) is a cellular based graft that contains mesenchymal stem cells (MSCs) and growth factors can confer osteogenic and osteoinductive potential to DBM. The goal of this study was to describe the outcome of DBM enriched with concentrated BMA in patients undergoing combined lumbar interbody and posterolateral fusion. METHODS: Eighty patients with a minimum of 12 months of follow-up were evaluated. Fusion and rates of complication were evaluated. Functional outcomes were assessed based on the modified Odom's criteria. Multiple logistic regression analysis was used to examine the effects of independent variables on fusion outcome. RESULTS: The overall rate of solid fusion (i.e patients with both solid posterolateral and interbody fusion) was 81.3% (65/80). Specifically, the radiographic evidence of solid posterolateral and interbody fusions were 81.3% (65/80) and 92.5% (74/80), respectively. Seven (8.75%) patients developed hardware-related complications, 2 (2.5%) patients developed a postoperative infection and 2 (2.5%) patients developed clinical pseudarthrosis. Charlson comorbidity index (CCI) scores of 3 and 4 were associated with non-solid unions (CCI-3, p = 0.048; CCI-4, p = 0.03). Excellent or good outcomes were achieved in 58 (72.5%) patients. CONCLUSIONS: Patients undergoing lumbar fusion using an enriched bone graft containing concentrated BMA added to DBM can achieve successful fusion with relatively low complications and good functional outcomes. Despite these findings, more studies with higher level of evidence are needed to better understand the efficacy of this promising graft option.

Perioperative Complications of Pedicle Subtraction Osteotomy.

Study Design Retrospective case series. Objective To describe the perioperative complications (0 to 90 days) associated with pedicle subtraction osteotomies (PSOs) performed at a tertiary spine center by two experienced spine surgeons who recently adopted the technique. Methods We reviewed all 65 patients (47 women and 18 men; mean age 60 years, range 24 to 80) who underwent a PSO at our institution. Descriptive data and analysis of complications were limited to the perioperative time (within 90 days of surgery). Data analyzed included operative time, length of stay (LOS), estimated blood loss (EBL), blood products, comorbidities, neurologic complications, and medical complications. Complications were rated as major and minor. Radiographic data was also analyzed. Results Ten patients (15.4%) had a major complication, and 15 (23%) had a minor complication. There were three perioperative deaths. The most common major complication was neurologic deficit (6.2%, 4/65), three with a permanent foot drop, and one with paraplegia secondary to postoperative hematoma. There were no differences between patients with and without a major complication in regard to age, gender, comorbidities, operative time, number of levels fused, and EBL (p > 0.05). Patients with a major complication had a longer intensive care unit stay (p = 0.04). There was no difference in the rate of major complications between the initial and later cases performed. Conclusion The major complication rate for pedicle subtraction osteotomy was 15% and the minor complication rate was 23%. The most common major complication was neurologic deficit in 6.2%. The complication rate did not change with increased surgeon experience.

Sagittal alignment changes and proximal junctional kyphosis in adolescent idiopathic scoliosis.

Commentary On Basques BA, Long WD, 3rd, Golinvaux NS, Bohl DD, Samuel AM, Lukasiewicz AM, et al. Poor visualization limits diagnosis of proximal junctional kyphosis in adolescent idiopathic scoliosis. Spine J 2015. doi:10.1016/j.spinee.2015.10.040.

Growth-Factor Nanocapsules That Enable Tunable Controlled Release for Bone Regeneration.

Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited by the short in vivo half-lives and the narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. In this research, a nanoscale controlled release system (degradable protein nanocapsule) is established via in situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes can be achieved with growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 nanocapsules.

A comparison of commercially available demineralized bone matrices with and without human mesenchymal stem cells in a rodent spinal fusion model.

OBJECTIVE The efficacy of some demineralized bone matrix (DBM) substances has been demonstrated in the spinal fusion of rats; however, no previous comparative study has reported the efficacy of DBM with human mesenchymal stem cells (hMSCs). There is an added cost to the products with stem cells, which should be justified by improved osteogenic potential. The purpose of this study is to prospectively compare the fusion rates of 3 different commercially available DBM substances, both with and without hMSCs. METHODS Posterolateral fusion was performed in 32 mature athymic nude rats. Three groups of 8 rats were implanted with 1 of 3 DBMs: Trinity Evolution (DBM with stem cells), Grafton (DBM without stem cells), or DBX (DBM without stem cells). A fourth group with no implanted material was used as a control group. Radiographs were obtained at 2, 4, and 8 weeks. The rats were euthanized at 8 weeks. Overall fusion was determined by manual palpation and micro-CT. RESULTS The fusion rates at 8 weeks on the radiographs for Trinity Evolution, Grafton, and DBX were 8 of 8 rats, 3 of 8 rats, and 5 of 8 rats, respectively. A significant difference was found between Trinity Evolution and Grafton (p = 0.01). The overall fusion rates as determined by micro-CT and manual palpation for Trinity Evolution, Grafton, and DBX were 4 of 8 rats, 3 of 8 rats, and 3 of 8 rats, respectively. The Trinity Evolution substance had the highest overall fusion rate, however no significant difference was found between groups. CONCLUSIONS The efficacies of these DBM substances are demonstrated; however, the advantage of DBM with hMSCs could not be found in terms of posterolateral fusion. When evaluating spinal fusion using DBM substances, CT analysis is necessary in order to not overestimate fusion.

Surgery for Degenerative Lumbar Scoliosis: The Development of Appropriateness Criteria.

STUDY DESIGN: The RAND/UCLA Appropriateness Method is a well-established means of developing criteria for assessing the appropriateness of surgery in specific subpopulations. It involves a systematic review of the literature and ratings by a multidisciplinary panel of national experts. OBJECTIVE: To evaluate the appropriateness of surgical interventions for degenerative lumbar scoliosis (DLS), including identifying clinical characteristics that influence when surgery is inappropriate, appropriate, or necessary, and which procedures are preferable. SUMMARY OF BACKGROUND DATA: DLS presents with diverse clinical symptoms and radiographic findings. Variability exists in both nonoperative and operative management. The appropriateness of surgery, and of specific surgical procedures, has not been defined for this important pathology of the aging spine. METHODS: We selected a panel of 11 experts, including surgical specialists from multiple disciplines. Next, we systematically reviewed relevant literature. Finally, in a three-round, modified-Delphi process, panelists rated the appropriateness and necessity of five different surgical procedures (dependent variables) on a nine-point scale for 260 different clinical scenarios that stratified patients according to age, medical comorbidities, symptoms, signs, and radiographic variables (independent variables). RESULTS: The 59 eligible studies identified via the systematic review were generally small or used weak designs. Panelists judged that surgery was generally appropriate for patients with at least moderate symptoms and larger or progressive deformities, moderate spinal or foraminal stenosis, or sagittal plane imbalance. Surgery was generally inappropriate for mild symptoms and smaller stable deformities, without sagittal imbalance or moderate stenosis, particularly among patients with advanced age and multiple comorbidities. For patients with larger or progressive deformities, imbalance, or severe multilevel stenosis, more extensive fusion and deformity correction procedures were generally preferred. CONCLUSION: Defining the appropriateness of surgery for patients with DLS will be useful to improve evidence-based clinical decision making as well as the consistency and quality of care for patients with DLS. LEVEL OF EVIDENCE: 3.

Kinetic magnetic resonance imaging analysis of lumbar segmental motion at levels adjacent to disc herniation.

PURPOSE: A retrospective radiographic study was carried out to analyze the effect of lumbar disc herniation on the kinetic motion of adjacent segments. METHODS: A total of 162 patients with low back pain or radicular pain in the lower limbs without a prior history of surgery were evaluated using kinetic magnetic resonance imaging. Translational motion, angular variation, and disc height were measured at each segment from L1-L2 to L5-S1. Other factors including the degree of disc degeneration, age, gender, and vertebral segment location were analyzed to determine any predisposing risk factors for segmental instability adjacent to disc herniations. RESULTS: Spinal levels above the disc herniation exhibited, on average, a 6.4 % increase in translational motion per mm of disc herniation (P = 0.496) and a 21.4 % increase in angular motion per mm herniation (P = 0.447). Levels below the herniation demonstrated a 5.2 % increase in translational motion per mm of disc herniation (P = 0.428) and a decrease of 10.7 % in angular motion per mm (P = 0.726). The degree of disc degeneration had no significant correlation with adjacent level motion. Similarly, disc herniation was not significantly correlated with disc height at adjacent levels, although there was a significant relationship between gender and adjacent segment disc height. CONCLUSIONS: Although disc height, translational motion, and angular variation are significantly affected at the level of a disc herniation, no significant changes are apparent in adjacent segments. Our results indicate that herniated discs have no effect on range of motion at adjacent levels regardless of the degree of disc degeneration or the size of disc herniation, suggesting that the natural progression of disc degeneration and adjacent segment disease may be separate, unrelated processes within the lumbar spine.

The Compensatory Relationship of Upper and Subaxial Cervical Motion in the Presence of Cervical Spondylosis.

STUDY DESIGN: This study was an in vivo kinematic magnetic resonance imaging analysis of cervical spinal motion in human subjects. OBJECTIVE: The objective of the study was to identify associations between disk degeneration in the subaxial cervical spine and upper cervical spinal motion in patients with general age-related cervical spondylosis. SUMMARY OF BACKGROUND DATA: The kinematic relationship between the occipital-atlantoaxial complex and subaxial cervical spine in patients with cervical spondylosis and decreased cervical motion is not well understood. METHODS: A total of 446 symptomatic patients who had neck pain with and without neurogenic symptoms were included in this study. Kinematic magnetic resonance imaging was performed with dynamic motion of the cervical spine in upright, weight-bearing neutral, flexion, and extension positions. Intervertebral disk degeneration for each segment from C2-3 to C7-T1 and sagittal angular motion between flexion and extension for each segment from Oc-C1 to C7-T1 was evaluated. Depending on the amount of sagittal subaxial angular motion, the patients were classified into 3 groups by sagittal angular motion using cutoff points based on tertile (<36-degree group: 149 cases; 36-47-degree group: 148 cases; and >47-degree group: 149 cases). RESULTS: A significant correlation was found between subaxial angular motion and intervertebral disk degeneration, indicating that the subaxial motion decreases according to the degree of disk degeneration. Mean angular motion of the occipital-atlantoaxial complex, especially of Oc-C1, was significantly higher in the <36-degree and 36-47-degree group than in the >47-degree group, whereas no significant difference was found at C1-C2. CONCLUSIONS: Our study demonstrates that decreased subaxial cervical spinal motion is associated with intervertebral disk degeneration in a symptomatic population. This decrease in mobility at the subaxial cervical spine is compensated for by an increase in angular mobility of the upper cervical spine at the occipital-atlantoaxial complex, especially at Oc-C1.