NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2-/- mice were protected from age-related OA development. Taken together, the TLR2-NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA.

Bone collagen quality in lumbar fusion patients: the association between volumetric bone mineral density and advanced glycation endproducts.

PURPOSE: The sole determination of volumetric bone mineral density (vBMD) is insufficient to evaluate overall bone integrity. The accumulation of advanced glycation endproducts (AGEs) stiffens and embrittles collagen fibers. Despite the important role of AGEs in bone aging, the relationship between AGEs and vBMD is poorly understood. We hypothesized that an accumulation of AGEs, a marker of impaired bone quality, is related to decreased vBMD. METHODS: Prospectively collected data of 127 patients undergoing lumbar fusion were analyzed. Quantitative computed tomography (QCT) measurements were performed at the lumbar spine. Intraoperative bone biopsies were obtained and analyzed with confocal fluorescence microscopy for fluorescent AGEs, both trabecular and cortical. Spearman's correlation coefficients were calculated to examine relationships between vBMD and fAGEs, stratified by sex. Multivariable linear regression analysis with adjustments for age, sex, body mass index (BMI), race, diabetes mellitus and HbA1c was used to investigate associations between vBMD and fAGEs. RESULTS: One-hundred and twenty-seven patients (51.2% female, 61.2 years, BMI of 28.7 kg/m2) with 107 bone biopsies were included in the final analysis, excluding patients on anti-osteoporotic drug therapy. In the univariate analysis, cortical fAGEs increased with decreasing vBMD at (r = -0.301; p = 0.030), but only in men. In the multivariable analysis, trabecular fAGEs increased with decreasing vBMD after adjusting for age, sex, BMI, race, diabetes mellitus and HbA1c (ß = 0.99;95%CI=(0.994,1.000); p = 0.04). CONCLUSION: QCT-derived vBMD measurements were found to be inversely associated with trabecular fAGEs. Our results enhance the understanding of bone integrity by suggesting that spine surgery patients with decreased bone quantity may also have poorer bone quality.

Preoperative MRI-based vertebral bone quality (VBQ) score assessment in patients undergoing lumbar spinal fusion.

BACKGROUND CONTEXT: The importance of bone status assessment in spine surgery is well recognized. The current gold standard for assessing bone mineral density is dual-energy X-ray absorptiometry (DEXA). However, DEXA has been shown to overestimate BMD in patients with spinal degenerative disease and obesity. Consequently, alternative radiographic measurements using data routinely gathered during preoperative evaluation have been explored for the evaluation of bone quality and fracture risk. Opportunistic quantitative computed tomography (QCT) and more recently, the MRI-based vertebral bone quality (VBQ) score, have both been shown to correlate with DEXA T-scores and predict osteoporotic fractures. However, to date the direct association between VBQ and QCT has not been studied. PURPOSE: The objective of this study was to evaluate the correlation between VBQ and spine QCT BMD measurements and assess whether the recently described novel VBQ score can predict the presence of osteopenia/osteoporosis diagnosed with QCT. STUDY DESIGN/SETTING: Cross-sectional study using retrospectively collected data. PATIENT SAMPLE: Patients undergoing lumbar fusion from 2014-2019 at a single, academic institution with available preoperative lumbar CT and T1-weighted MRIs were included. OUTCOME MEASURES: Correlation of the VBQ score with BMD measured by QCT, and association between VBQ score and presence of osteopenia/osteoporosis. METHODS: Asynchronous QCT measurements were performed. The average L1-L2 BMD was calculated and patients were categorized as either normal BMD (>120 mg/cm3) or osteopenic/osteoporotic (≤120 mg/cm3). The VBQ score was calculated by dividing the median signal intensity of the L1-L4 vertebral bodies by the signal intensity of the cerebrospinal fluid on midsagittal T1-weighted MRI images. Inter-observer reliability testing of the VBQ measurements was performed. Demographic data and the VBQ score were compared between the normal and osteopenic/osteoporotic group. To determine the area-under-curve (AUC) of the VBQ score as a predictor of osteopenia/osteoporosis receiver operating characteristic (ROC) analysis was performed. VBQ scores were compared with QCT BMD using the Pearson's correlation. RESULTS: A total of 198 patients (53% female) were included. The mean age was 62 years and the mean BMI was 28.2 kg/m2. The inter-observer reliability of the VBQ measurements was excellent (ICC of 0.90). When comparing the patients with normal QCT BMD to those with osteopenia/osteoporosis, the patients with osteopenia/osteoporosis were significantly older (64.9 vs. 56.7 years, p<.0001). The osteopenic/osteoporotic group had significantly higher VBQ scores (2.6 vs. 2.2, p<.0001). The VBQ score showed a statistically significant negative correlation with QCT BMD (correlation coefficient = -0.358, 95% CI -0.473 - -0.23, p<.001). Using a VBQ score cutoff value of 2.388, the categorical VBQ score yielded a sensitivity of 74.3% and a specificity of 57.0% with an AUC of 0.7079 to differentiate patients with osteopenia/osteoporosis and with normal BMD. CONCLUSIONS: We found that the VBQ score showed moderate diagnostic ability to differentiate patients with normal BMD versus osteopenic/osteoporotic BMD based on QCT. VBQ may be an interesting adjunct to clinically performed bone density measurements in the future.

Effects of an opioid stewardship program on opioid consumption and related outcomes after multilevel lumbar spine fusion: a pre- and postimplementation analysis of 268 patients.

OBJECTIVE: Opioid stewardship programs combine clinical, regulatory, and educational interventions to minimize inappropriate opioid use and prescribing for orthopedic and spine surgery. Most evaluations of stewardship programs quantify effects on prescriber behavior, whereas patient-relevant outcomes have been relatively neglected. The authors evaluated the impact of an opioid stewardship program on perioperative opioid consumption, prescribing, and related clinical outcomes after multilevel lumbar fusion. METHODS: The study was based on a retrospective, quasi-experimental, pretest-posttest design in 268 adult patients who underwent multilevel lumbar fusion in 2016 (preimplementation, n = 141) or 2019 (postimplementation, n = 127). The primary outcome was in-hospital opioid consumption (morphine equivalent dose [MED], mg). Secondary outcomes included numeric rating scale pain scores (0-10), length of stay (LOS), incidence of opioid-induced side effects (gastrointestinal, nausea/vomiting, respiratory, sedation, cognitive), and preoperative and discharge prescribing. Outcomes were measured continuously during the hospital admission. Differences in outcomes between the epochs were assessed in bivariable (Wilcoxon signed-rank or Fisher's exact tests) and multivariable (Wald's chi-square test) analyses. RESULTS: In bivariable analyses, there were significant decreases in preoperative opioid use (46% vs 28% of patients, p = 0.002), preoperative opioid prescribing (MED 30 mg [IQR 20-60 mg] vs 20 mg [IQR 11-39 mg], p = 0.003), in-hospital opioid consumption (MED 329 mg [IQR 188-575 mg] vs 199 mg [100-372 mg], p < 0.001), the incidence of any opioid-related side effect (62% vs 50%, p = 0.03), and discharge opioid prescribing (MED 90 mg [IQR 60-135 mg] vs 60 mg [IQR 45-80 mg], p < 0.0001) between 2016 and 2019. There were no significant differences in postanesthesia care unit pain scores (4 [IQR 3-6] vs 5 [IQR 3-6], p = 0.33), nursing floor pain scores (4 [IQR 3-5] vs 4 [IQR 3-5], p = 0.93), or total LOS (118 hours [IQR 81-173 hours] vs 103 hours [IQR 81-132 hours], p = 0.21). On multivariable analysis, the opioid stewardship program was significantly associated with decreased discharge prescribing (Wald's chi square = 9.45, effect size -52.4, 95% confidence interval [CI] -86 to -19.0, p = 0.002). The number of lumbar levels fused had the strongest effect on total opioid consumption during the hospital stay (Wald's chi square = 16.53, effect size = 539, 95% CI 279.1 to 799, p < 0.001), followed by preoperative opioid use (Wald's chi square = 44.04, effect size = 5, 95% CI 4 to 7, p < 0.001). CONCLUSIONS: A significant decrease in perioperative opioid prescribing, consumption, and opioid-related side effects was found after implementation of an opioid stewardship program. These gains were achieved without adverse effects on pain scores or LOS. These results suggest the major impact of opioid stewardship programs for spine surgery may be on changing prescriber behavior.

The cervical spine demonstrates less postoperative bone loss than the lumbar spine.

The objective of this study is to determine the bone mineral density (BMD) changes in adjacent vertebra following anterior cervical discectomy and fusion (ACDF). Consecutive patients undergoing ACDF with available preoperative and postoperative computed tomography (CT) imaging were included. Quantitative CT measurements of screw-free cervical and first thoracic vertebra were performed. Comparisons between pre- and postoperative BMD in the vertebrae one or two levels above the upper instrumented vertebra (UIV + 1, UIV + 2) and one level below the lowest instrumented vertebra (LIV + 1) were assessed. Seventy-two patients (men, 66.7%) met the inclusion criteria. The patient population was 91.7% Caucasian with a mean age of 55.0 years. The mean interval (±SD) between surgery and secondary CT was 157 ± 23 days. Preoperative BMD (±SD) in UIV + 1 was 300.6 ± 66.2 mg/cm3 . There was a significant BMD loss of 1.5% at UIV + 1 after surgery, resulting in a postoperative BMD of 296.2 ± 64.8 mg/cm3 (p = .029). At UIV + 2 and LIV + 1, no significant differences between pre- and postoperative BMD (304.7 ± 75.7 mg/cm3 vs. 299.8 ± 74.3 mg/cm3 , 197.3 ± 50.4 mg/cm3 vs. 200.8 ± 48.7 mg/cm3 , p = .113 and p = .078, respectively) were observed. Clinical significance Our results demonstrate a small BMD decrease of 1.5% at UIV + 1. This suggests that the effect of ACDF surgery on the adjacent levels might be smaller compared to the previously described lumbar BMD loss of 10%-20% following posterior lumbar fusion procedures.

Spinal Cord Medial Safe Zone for C2 Pedicle Instrumentation: An MRI Measurement Analysis.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: The aim of this study was to investigate the spinal cord safety margins for C2 instrumentation. SUMMARY OF BACKGROUND DATA: Intraoperative spinal cord injury during C2 spine surgery is a rare, but potentially life-threatening complication. Preoperative planning for C2 instrumentation mainly focuses on C2 pedicle bony dimensions on CT and the vertebral artery location and few studies have evaluated C2 spinal cord safety margins. METHODS: We measured two distances in C2 bilaterally: C2 pedicle to dura distance (P-D), defined as a transverse line that measured the shortest distance between the medial wall of the C2 pedicle and the dural sac, and C2 pedicle to spinal cord (P-SC), defined as a transverse line that measured the shortest distance between the medial wall of the C2 pedicle and spinal cord. We defined the distances >4 mm as safe for instrumentation. RESULT: A total of 146 patients (mean age 71.2, 50.7% female) were included. The average distances were 5.5 mm for C2 left PD, 5.9 mm for C2 right P-D, 10.1 mm for C2 left P-SC, and 10.6 mm for C2 right P-SC. Twenty-eight (21.4%) patients had C2 P-D distances <4 mm and of those two (7%) patients had distances <2 mm. There were more female patients with C2 P-D distances under 4 mm compared to males. No patient had C2 P-SC distances <4 mm. CONCLUSION: We demonstrated that around 20% of patients had C2 P-D distance <4 mm, but no patient had C2 P-SC distance <4 mm. Since a lateral misplacement can lead to a potentially fatal vertebral artery injury, medial screw trajectory is recommended for C2 pedicle instrumentation with consideration of these safety margins.Level of Evidence: 3.

Future Perspectives in Spinal Cord Repair: Brain as Saviour? TSCI with Concurrent TBI: Pathophysiological Interaction and Impact on MSC Treatment.

Traumatic spinal cord injury (TSCI), commonly caused by high energy trauma in young active patients, is frequently accompanied by traumatic brain injury (TBI). Although combined trauma results in inferior clinical outcomes and a higher mortality rate, the understanding of the pathophysiological interaction of co-occurring TSCI and TBI remains limited. This review provides a detailed overview of the local and systemic alterations due to TSCI and TBI, which severely affect the autonomic and sensory nervous system, immune response, the blood-brain and spinal cord barrier, local perfusion, endocrine homeostasis, posttraumatic metabolism, and circadian rhythm. Because currently developed mesenchymal stem cell (MSC)-based therapeutic strategies for TSCI provide only mild benefit, this review raises awareness of the impact of TSCI-TBI interaction on TSCI pathophysiology and MSC treatment. Therefore, we propose that unravelling the underlying pathophysiology of TSCI with concomitant TBI will reveal promising pharmacological targets and therapeutic strategies for regenerative therapies, further improving MSC therapy.

Workers' Compensation Status in Association with a High NDI Score Negatively Impacts Post-Operative Dysphagia and Dysphonia Following Anterior Cervical Fusion.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a safe and effective procedure but has approach-related complications like postoperative dysphagia and dysphonia (PDD). Patient-reported outcome measures including the Hospital for Special Surgery Dysphagia and Dysphonia Inventory (HSS-DDI) have been used for the assessment of PDD. Various factors have been described that affect ACDF outcomes, and our aim was to investigate the effect of workers' compensation (WC) status. METHODS: We included patients who underwent ACDF from 2015 to 2018 stratified according to insurance status: WC/non-WC. PDDs were assessed using the HSS-DDI score. We conducted logistic regression analyses. Statistical significance was set at P < 0.05. RESULTS: We included 287 patients, 44 (15.33%) WC and 243 (84.67%) non-WC. A statistical comparison revealed a clinically relevant difference in the HSS-DDI total score and both subdomains (P = 0.015; dysphagia P = 0.021; dysphonia P = 0.002). Additional logistic regression analysis adjusting for preoperative Neck Disability Index scores resulted in no clinically relevant differences in the HSS-DDI total score and both subdomains (total score P = 0.420; dysphagia P = 0.531; dysphonia 0.315). CONCLUSIONS: WC status was associated with a worse HSS-DDI score but could not be shown to be an independent risk factor for PDD. The preoperative NDI score was a strong predictor for PDD with a clinically relevant difference in the HSS DDI score (P < 0.0001). Surgeon awareness of risk factors for PDD such as WC status, even if it could not be shown as independent, is important as it may influence surgical decision making and managing patient expectations.

Thoracic bone mineral density measured by quantitative computed tomography in patients undergoing spine surgery.

BACKGROUND CONTEXT: The thoracic spine is a common location for vertebral fractures as well as instrumentation failure after long spinal fusion procedures. The association between those complications and bone mineral density (BMD) are well recognized. Due to the overlying sternum and ribs in the thoracic spine, projectional BMD assessment tools such as dual energy x-ray absorptiometry (DXA) are limited to the lumbar spine. Quantitative computed tomography circumvents several shortcomings of DXA and allows for level-specific BMD measurements. Studies comprehensively quantifying BMD of the entire thoracic spine in patients undergoing spine surgery are limited. PURPOSE: The objective of this study was: (1) to assess the reliability of thoracic QCT measurements, (2) to determine possible level-specific BMD variation throughout the thoracic spine and (3) to assess the correlation between BMDs of the T1-T12 spinal levels. STUDY DESIGN/SETTING: Cross-sectional observation study. PATIENT SAMPLE: Patients undergoing spine surgery from 2016-2020 at a single, academic institution with available preoperative CT imaging of the thoracic spine were included in this study. OUTCOME MEASURES: The outcome measure was BMD measured by QCT. METHODS: Patients undergoing spine surgery from 2016-2020 at a single, academic institution with available preoperative CT imaging of the thoracic spine were included in this study. Subjects with previous instrumentation at any thoracic level, concurrent vertebral fractures, a Cobb angle of more than 20 degrees, or incomplete thoracic spine CT imaging were excluded. Asynchronous quantitative computed tomography (QCT) measurements of T1-T12 were performed. To assess inter- and intra-observer reliability, a validation study was performed on 120 vertebrae in 10 randomly selected patients. The interclass correlation coefficient (ICC) was calculated. A pairwise comparison of BMD was conducted and correlations between each thoracic level were evaluated. The statistical significance level was set at p<.05. RESULTS: 60 patients (men, 51.7%) met inclusion criteria. The study population was 90% Caucasian with a mean age of 62.2 years and a mean BMI of 30.2 kg/m2. The inter- and intra-observer reliability of the thoracic QCT measurements was excellent (ICC of 0.97 and 0.97, respectively). The trabecular BMD was highest in the upper thoracic spine and decreased in the caudal direction (T1 = 182.3 mg/cm3, T2 = 168.1 mg/cm3, T3 = 163.5 mg/cm3, T4 = 164.7 mg/cm3, T5 = 161.4 mg/cm3, T6 = 152.5 mg/cm3, T7 = 143.5 mg/cm3, T8 = 141.3 mg/cm3, T9 = 143.5 mg/cm3, T10 = 145.1 mg/cm3, T11 = 145.3 mg/cm3, T12 = 133.6 mg/cm3). The BMD of all thoracic levels cranial to T6 was statistically higher than the BMD of all levels caudal to T6 (p < .001). Nonetheless, significant correlations in BMD among all measured thoracic levels were observed, with a Pearson's correlation coefficient ranging from 0.74 to 0.97. CONCLUSIONS: There is significant regional BMD variation in the thoracic spine depending on spinal level. This BMD variation might contribute to several clinically relevant phenomena. First, vertebral fractures occur most commonly at the thoracolumbar junction including T12. In addition to mechanical reasons, these fractures might be partially attributed to thoracic BMD that is lowest at T12. Second, the optimal upper instrumented vertebra (UIV) for stopping long fusions to the sacrum and pelvis is controversial. The BMD of surgically relevant upper thoracic stopping points (T2-T4) was significantly higher than the BMD of lower thoracic stopping points (T10-T12). Besides stress concentration at the relatively mobile lower thoracic segments, the low BMD at these levels might contribute to previously suggested higher rates of junctional failures with short fusions.

The association of transversus abdominis plane block with length of stay, pain and opioid consumption after anterior or lateral lumbar fusion: a retrospective study.

PURPOSE: Anterior (ALIF) and lateral (LLIF) lumbar interbody fusion is associated with significant postoperative pain, opioid consumption and length of stay. Transversus abdominis plane (TAP) blocks improve these outcomes in other surgical subtypes but have not been applied to spine surgery. A retrospective study of 250 patients was performed to describe associations between TAP block and outcomes after ALIF/LLIF. METHODS: The electronic medical records of 129 patients who underwent ALIF or LLIF with TAP block were compared to 121 patients who did not. All patients were cared for under a standardized perioperative care pathway with comprehensive multimodal analgesia. Differences in patent demographics, surgical factors, length of stay (LOS), opioid consumption, opioid-related side effects and pain scores were compared in bivariable and multivariable regression analyses. RESULTS: In bivariable analyses, TAP block was associated with a significantly shorter LOS, less postoperative nausea/vomiting and lower opioid consumption in the post-anesthesia care unit (PACU). In multivariable analyses, TAP block was associated with significantly shorter LOS (ß - 12 h, 95% CI (- 22, - 2 h); p = 0.021). Preoperative opioid use was a strong predictive factor for higher opioid consumption in the PACU, opioid use in the first 24 h after surgery and longer LOS. We did not find significant differences in pain scores at any times between the groups. CONCLUSION: TAP block may represent an effective addition to pain management and opioid-reducing strategies and improve outcomes after ALIF/LLIF. Prospective trials are warranted to further explore these associations.

Endplate volumetric bone mineral density is a predictor for cage subsidence following lateral lumbar interbody fusion: a risk factor analysis.

BACKGROUND CONTEXT: It has been reported in previous studies that a decreased bone mineral density (BMD) as measured by dual X-ray absorptiometry (DXA) is associated with subsidence. However, there is limited research on the role of volumetric BMD (vBMD) as measured by quantitative computed tomography (QCT). Further, metabolic conditions such as obesity and type 2 diabetes have been associated with poor bone quality, but the impact of these metabolic conditions on on subsidence rates following lateral lumbar interbody fusion (LLIF) remains unclear. As such, risk factors for subsidence following LLIF is an area of ongoing research. PURPOSE: The purpose of this study is to identify risk factors for subsidence following LLIF with a focus on metabolic conditions and vBMD as measured by QCT. STUDY DESIGN/SETTING: Retrospective cohort study at a single academic institution. PATIENT SAMPLE: Consecutive patients undergoing LLIF with or without posterior screws from 2014 to 2019 at a single academic institution who had a pre-operative CT and radiological imaging including radiographs or CT scans between 5 and 14 months post-operatively to assess for cage subsidence. OUTCOME MEASURE: Subsidence prevalence following LLIF. METHODS: We reviewed patients undergoing LLIF with or without posterior screws from 2014 to 2019 with a follow-up ≥5 months. Cage subsidence was assessed using the grading system by Marchi et al. Endplate volumetric BMD (EP-vBMD), vertebral bone volumetric BMD (VB-vBMD), BMI, and diabetes status were measured. Univariable analysis and multivariable logistic regression analyses with a generalized mixed model were conducted. Ad hoc analysis, including receiver operative characteristic curve analysis, was used for identifying the cut-off values in significant continuous variables for subsidence. Chi-Squared and ANOVA tests were used for categorical comparisons. RESULTS: Five hundred sixty-seven levels in 347 patients were included in the final analysis. Mean age (± SD) was 61.7 ± 11.1yrs, 50.3% were male, and 89.6% were Caucasian. Subsidence was observed in 160 levels (28.2%). Multivariable analysis demonstrated an absence of posterior screws [OR = 2.854 (1.483 - 5.215), p=.001] and decreased EP-vBMD [0.996 (0.991 - 1.000), p=.032] were associated with an increased risk of subsidence. Increased BMI and diabetes status were not associated with increased rates of subsidence. Patients without posterior screws and low EP-vBMD experienced subsidence at 44.9% of levels. CONCLUSIONS: Our results demonstrated that decreased EP-vBMD and standalone status were significantly associated with increased rates of subsidence following LLIF independent of BMI or diabetes status. Further analysis demonstrated that patients with a decreased EP-vBMD and without posterior screws experienced subsidence nearly 2.5 times higher than patients with no risk factors. In patients with a low EP-vBMD undergoing LLIF, posterior screws should be considered.

Determinants of Postoperative Spinal Height Change among Adult Spinal Deformity Patients with Long Construct Circumferential Fusion.

STUDY DESIGN: Retrospective clinical study. PURPOSE: To describe postoperative height changes and identify the predictive factors of spinal height (SH) changes among patients with adult spinal deformity (ASD) who underwent circumferential lumbar fusion with instrumentation. OVERVIEW OF LITERATURE: Postoperative height changes remain an important issue after spinal fusion surgery that affects the overall satisfaction with surgery. Previous studies of postoperative height change have focused exclusively on young patients with adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively reviewed the clinical and imaging data of ASD patients who underwent lumbar corrective circumferential fusion of ≥3 levels (n=106). SH was defined as the vertical distance between C2 and S1 on a standing lateral image. As potential predictors of postoperative height change, the number of lateral lumbar interbody fusion (LLIF) levels, change in spino-pelvic parameters, total number of levels fused, and pedicle subtraction osteotomies (PSO) were documented. Univariate and multivariate linear regression analyses were performed to identify the predictors of postoperative height change. RESULTS: The mean SH change was -2.39±50.8 mm (range, -160 to 172 mm). The univariate analyses showed that the number of LLIF levels (coefficient=10.9, p=0.03), the absolute coronal vertical axis change (coefficient=0.6, p=0.01), and the absolute Cobb angle change (coefficient=-0.9, p=0.03) were significant predictors for height change. Patients with PSOs (n=14) tended to have a shorter height postoperatively (coefficient=-26.1); however, this difference was not significant (p=0.07). Multivariate analyses conducted with variables of p<0.20 showed that pelvic tilt (PT) change is an independent contributor to SH change (coefficient=-0.99, p=0.04, R2=0.11). CONCLUSIONS: Utilizing a modified definition of SH used in previous AIS studies, we demonstrated that patients with ASD lose SH postoperatively and that PT change was an independent contributor of SH change.

The effect of obesity, diabetes, and epidural steroid injection on regional volumetric bone mineral density measured by quantitative computed tomography in the lumbosacral spine.

PURPOSE: High body mass index (BMI) is positively correlated with bone mineral density (BMD) in healthy adults; however, the effect of BMI on regional segmental BMDs in the axial skeleton is unclear. In addition, obese patients often have glucose intolerance and patients with lumbar spine pathology commonly have a history of epidural steroid injections (ESIs). The purpose of this study is to evaluate the effect of these patient factors on regional differences in BMD measured by quantitative computed tomography (QCT) in a lumbar fusion patient cohort. METHODS: The data were obtained from a database comprised of clinical and preoperative CT data from 296 patients who underwent primary posterior lumbar spinal fusion from 2014 to 2017. QCT-vBMDs of L1 to L5, S1 body, and sacral alae were measured. Multivariate linear regression analyses were performed with setting vBMDs as the response variables. As explanatory variables, age, sex, race, current smoking, categorized BMI, diabetes, and ESI were chosen a priori. RESULTS: A total of 260 patients were included in the final analysis. Multivariate analyses demonstrated that obese and morbidly obese patients had significantly higher vBMD in the sacral alae (SA). Diabetes showed independent positive associations with vBMDs in L1, L2, and the SA. Additionally, patients with an ESI history demonstrated significantly lower vBMD in the SA. CONCLUSIONS: Our results demonstrate that obesity, diabetes, and epidural steroids affected vBMD differently by lumbosacral spine region. The vBMD of the SA appeared to be more sensitive to various patient factors than other lumbar regions.

Expectations of Lumbar Surgery Outcomes among Opioid Users Compared with Non-Users.

STUDY DESIGN: Matched cohort study. PURPOSE: To compare and describe the effect of opioid usage on the expectations of lumbar surgery outcomes among patients taking opioids and patients not taking opioids. OVERVIEW OF LITERATURE: Chronic opioid use is common among lumbar-spine surgery patients. The decision to undergo elective lumbar surgery is influenced by the expected surgery outcomes. However, the effects of opioids on patients' expectations of lumbar surgery outcomes remain to be rigorously assessed. METHODS: A total of 77 opioid users grouped according to dose and duration (54 "higher users," 30 "lower users") were matched 2:1 to 154 non-opioid users based on age, sex, marital status, chiropractic care, disability, and diagnosis. All patients completed a validated 20-item Expectations Survey measuring expected improvement with regard to symptoms, function, psychological well-being, and anticipated future spine condition. "Greater expectations" was defined as a higher survey score (possible range, 0-100) based on the number of items expected and degree of improvement expected. RESULTS: The mean Expectations Survey scores for all opioid users and all non-users were similar (73 vs. 70, p=0.18). Scores were different, however, for lower users (79) compared with matched non-users (69, p=0.01) and compared with higher users (70, p=0.01). In multivariable analysis, "reater expectations" was independently associated with having had chiropractic care (p=0.03), being more disabled (p=0.002), and being a lower-dose opioid user (p=0.03). Compared with higher users, lower users were also more likely to expect not to need pain medications 2 years after surgery (47% vs. 83%, p=0.003). CONCLUSIONS: Patient expectations of lumbar surgery are associated with diverse demographic and clinical variables. A lower dose and shorter duration of opioid use were associated with expecting more items and expecting more complete improvement compared with non-users. In addition, lower opioid users had greater overall expectations compared with higher users.

The Association Between Endplate Changes and Risk for Early Severe Cage Subsidence Among Standalone Lateral Lumbar Interbody Fusion Patients.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to investigate the association of Modic type endplate changes with the risk of severe subsidence after standalone lateral lumbar interbody fusion (SA-LLIF). SUMMARY OF BACKGROUND DATA: It has been reported that certain endplate radiolographic features are associated with higher regional bone mineral density (BMD) in the adjacent vertebrae in the lumbar spine. It remains unclear whether these changes have protective effects against osteoporotic complications such as cage subsidence after lumbar surgery. METHODS: We reviewed patients undergoing SA-LLIF from 2007 to 2016 with a follow-up >6 months. Cage subsidence was assessed utilizing the grading system by Marchi et al. As potential contributing factors for cage subsidence, we measured the endplate volumetric BMD (EP-vBMD) and the standard trabecular volumetric BMD measurement in the vertebral body. Modic changes (MC) on magnetic resonance imaging were measured as a qualitative factor for endplate condition. Univariate analysis and multivariate logistic regression analyses with a generalized mixed model were conducted. RESULTS: Two hundred six levels in 97 patients were included in the final analysis. Mean age (± SD) was 66.7 ±â€Š10.7. Sisty-sdpercent of the patients were female. Severe subsidence was observed in 66 levels (32.0%). After adjusting for age, bone morphogenetic protein (BMP) use, and number of levels fused, the presence of MC type 2 was significantly associated with lower risk of severe subsidence (OR = 0.28 [0.09-0.88], P = 0.029). Whereas, EP-vBMD did not demonstrate a statistical significance (p = 0.600). CONCLUSION: The presence of a Modic type 2 change was significantly associated with lower odds of severe subsidence after SA-LLIF. Nonetheless, this significant association was independent from regional EP-vBMD values. This finding suggests that microstructural and/or material property changes associated with Modic type 2 changes might have a protective effect in this patient population. LEVEL OF EVIDENCE: 4.

Prevalence of osteoporosis and osteopenia diagnosed using quantitative CT in 296 consecutive lumbar fusion patients.

OBJECTIVE: Osteoporosis is a metabolic bone disease that increases the risk for fragility fractures. Screening and diagnosis can be achieved by measuring bone mineral density (BMD) using quantitative CT tomography (QCT) in the lumbar spine. QCT-derived BMD measurements can be used to diagnose osteopenia or osteoporosis based on American College of Radiology (ACR) thresholds. Many reports exist regarding the disease prevalence in asymptomatic and disease-specific populations; however, osteoporosis/osteopenia prevalence rates in lumbar spine fusion patients without fracture have not been reported. The purpose of this study was to define osteoporosis and osteopenia prevalence in lumbar fusion patients using QCT. METHODS: A retrospective review of prospective data was performed. All patients undergoing lumbar fusion surgery who had preoperative fine-cut CT scans were eligible. QCT-derived BMD measurements were performed at L1 and L2. The L1-2 average BMD was used to classify patients as having normal findings, osteopenia, or osteoporosis based on ACR criteria. Disease prevalence was calculated. Subgroup analyses based on age, sex, ethnicity, and history of abnormal BMD were performed. Differences between categorical groups were calculated with Fisher's exact test. RESULTS: Overall, 296 consecutive patients (55.4% female) were studied. The mean age was 63 years (range 21-89 years). There were 248 (83.8%) patients with ages ≥ 50 years. No previous clinical history of abnormal BMD was seen in 212 (71.6%) patients. Osteopenia was present in 129 (43.6%) patients and osteoporosis in 44 (14.9%). There were no prevalence differences between sex or race. Patients ≥ 50 years of age had a significantly higher frequency of osteopenia/osteoporosis than those who were < 50 years of age. CONCLUSIONS: In 296 consecutive patients undergoing lumbar fusion surgery, the prevalence of osteoporosis was 14.9% and that for osteopenia was 43.6% diagnosed by QCT. This is the first report of osteoporosis disease prevalence in lumbar fusion patients without vertebral fragility fractures diagnosed by QCT.

Regional bone mineral density differences measured by quantitative computed tomography in patients undergoing anterior cervical spine surgery.

BACKGROUND CONTEXT: Clinically, the association between bone mineral density (BMD) and surgical instrumentation efficacy is well recognized. Although several studies have quantified the BMD of the human lumbar spine, comprehensive BMD data for the cervical spine is limited. The few available studies included young and healthy patient samples, which may not represent the typical cervical fusion patient. Currently no large scale study provides detailed BMD information of the cervical and first thoracic vertebrae in patients undergoing anterior cervical spine surgery. PURPOSE: The objective of this study was to determine possible trabecular BMD variations throughout the cervical spine and first thoracic vertebra in patients undergoing anterior cervical discectomy and fusion (ACDF) and to assess the correlation between BMDs of the spinal levels C1-T1. STUDY DESIGN/SETTING: This is a retrospective case series. PATIENT SAMPLE: Patients undergoing ACDF from 2015 to 2018 at a single, academic institution with available preoperative CT imaging were included in this study. OUTCOME MEASURES: The outcome measure was BMD measured by QCT. METHODS: Patients that underwent ACDF from 2015 to 2018 at a single, academic institution were included in this study. Subjects with previous cervical instrumentation or missing/incomplete preoperative cervical spine CT imaging were excluded. Asynchronous quantitative computed tomography (QCT) measurements of the lateral masses of C1 and the C2-T1 vertebral bodies were performed. For this purpose, an elliptical region of interest that consisted exclusively of trabecular bone was selected. Any apparent sclerotic levels that might affect trabecular QCT measurements were excluded from the final analysis. Interobserver reliability of measurements was assessed by calculating the interclass correlation coefficients (ICC). Pairwise comparison of BMD was performed and correlations between the various cervical levels were evaluated. The statistical significance level was set at p<.05. RESULTS: In all, 194 patients (men, 62.9%) met inclusion criteria. The patient population was 91.2% Caucasian with a mean age of 55.9 years and mean BMI of 28.2 kg/m2. The ICC of cervical QCT measurements was excellent (ICC 0.92). The trabecular BMD was highest in the mid-cervical spine (C4) and decreased in the caudal direction (C1 average=253.3 mg/cm3, C2=276.6 mg/cm3, C3=272.2 mg/cm3, C4=283.5 mg/cm3, C5=265.1 mg/cm3, C6=235.3 mg/cm3, C7=216.8 mg/cm3, T1=184.4 mg/cm3). The BMD of C7 and T1 was significantly lower than those of all other levels. Nonetheless, significant correlations in BMD among all measured levels were observed, with a Pearson's correlation coefficient ranging from 0.507 to 0.885. CONCLUSIONS: To the authors' knowledge this is the largest study assessing trabecular BMD of the entire cervical spine and first thoracic vertebra by QCT. The patient sample consisted of patients undergoing ACDF, which adds to the clinical relevance of the findings. Knowledge of BMD variation in the cervical spine might be useful to surgeons utilizing anterior cervical spine plate and screw systems. Due to the significant variation in cervical BMD, procedures involving instrumentation at lower density caudal levels might potentially benefit from a modification in instrumentation or surgical technique to achieve results similar to more cephalad levels.

Trends in lumbar spinal fusion-a literature review.

Over the past several decades, there has been an upward trend in the total number of spinal fusion procedures worldwide. Advanced spinal fusion techniques with or without internal fixation, additional innovations in surgical approaches, innovative implants including a wide variety of interbody devices, and new alternatives in bone grafting materials are some reasons for the increasing number of spine fusion procedures. Moreover, the indications for spinal fusion have broadened over time. Initially developed for the treatment of instability and deformity due to tuberculosis, scoliosis, and traumatic injury, spinal fusion surgery has now a wide range of indications like spondylolisthesis, congenital or degenerative deformity, spinal tumors, and pseudarthrosis, with degenerative disorders as the most common indication. This review emphasizes current lumbar fusion techniques and their development in the past decades.

Hemodynamically significant cardiac arrhythmias during general anesthesia for spine surgery: A case series and literature review.

BACKGROUND CONTEXT: Hemodynamically significant bradycardia and cardiac arrest (CA) are rare under general anesthesia (GA) for spine surgery. Although patient risks are well defined, emerging data implicate surgical, anesthetic and neurologic factors which should be considered in the immediate management and decision to continue or terminate surgery. PURPOSE: To characterize causes and contributors to significant arrhythmias during spine surgery. We also provide an updated literature review to inform spine care teams and aid in the management of intraoperative bradycardia and CA. STUDY DESIGN: Case series and literature review. PATIENT SAMPLE: Six patients who underwent spine surgery from 03/2016 to 01/2020 at a single institution and developed unexpected hemodynamically significant arrhythmia. OUTCOME MEASURES: Our primary outcome was to identify potential risk factors of interest for significant arrhythmia during spine surgery. METHODS: Medical records of patients who underwent spine surgery from 03/2016 to 01/2020 at a single institution and developed unexpected hemodynamically significant arrhythmia during spine surgery were identified from a departmental Quality Assurance Database. We evaluated the presence/absence of patient, surgical, anesthetic and neurologic risk factors and estimated the most likely etiology of the event, immediate and subsequent management, whether surgery was postponed or continued and outcomes. RESULTS: We found a temporal relationship of bradyarrhythmia and CA after somatosensory evoked potential (SSEP) stimulation in 4/6 cases and pharmacy/polypharmacy in 2/6. Surgery was completed in 4/6 patients, and terminated in 2/6 (subsequently completed in both). We found no adverse outcomes in any patients. Our literature review predominately identified case reports for guidance to support decision making. New literaure suggests peripheral nerve blocks and opioid-sparing anesthetic agents should also be considered. CONCLUSIONS: Significant bradycardia and CA during spine surgery does not always require termination of the surgical procedure. Decision making should be undertaken in each case individually, with an updated awareness of potential causes. The study also suggests the need for large prospective studies to adequately assess incidence, risk factors and outcomes.