Diagnosis of spine pseudoarthrosis based on the biomechanical properties of bone.

BACKGROUND CONTEXT: Failure to fuse following anterior cervical discectomy and fusion (ACDF) may result in symptomatic pseudoarthrosis. Traditional diagnosis involves computerized tomography to detect bridging bone and/or flexion-extension radiographs to assess whether segmental motion is above specific thresholds; however, there are currently no well-validated diagnostic tests. We propose a biomechanically rational approach to achieve a reliable diagnostic test for pseudoarthrosis. PURPOSE: Develop and test a biomechanically based approach to the diagnosis of pseudoarthrosis. STUDY DESIGN: Literature review, development of theory, re-analysis of a previously published study with surgical exploration as the gold-standard, and retrospective analysis of pooled studies to understand time to fusion. METHODS: Fully automated methods were used to measure disc space strains (change in disc space height divided by initial height). Measurement error combined with the reported failure strain of trabecular bone led to a proposed strain threshold for diagnosis of pseudoarthrosis following ACDF. We reanalyzed previously reported flexion-extension radiographs for asymptomatic volunteers to assess whether flexion-extension radiographs, in the absence of fusion surgery, can be expected to provide sufficient stress on motion segments to allow for reliable strain-based fusion assessment. The sensitivity and specificity of strain- and rotation-based pseudoarthrosis diagnosis were assessed by reanalysis of previously reported post-ACDF flexion-extension radiographs, where intraoperative fusion assessments were also available. Finally, we assessed changes in strain over time using 9,869 flexion-extension radiographs obtained 6 weeks to 84 months post-ACDF surgery from 1,369 patients. RESULTS: The estimated error in automated measurement of disc space strain from radiographs was approximately 3%, and the reported failure strain of bridging bone was less than 2.5%. On that basis, we propose a 5% strain threshold for pseudoarthrosis diagnosis. Reanalysis of a study in which intraoperative fusion assessments were available revealed 67% sensitivity and 82% specificity for strain-based diagnosis of pseudoarthrosis, which was comparable to rotation-based diagnosis. Analysis of post-ACDF flexion-extension radiographs revealed rapid strain reduction for up to 24 months, followed by a slower decrease for up to 84 months. When rotation is less than 2 degrees, the strain-based diagnosis differed from the rotation-based diagnosis in approximately 14% of the cases. CONCLUSIONS: We propose steps for standardizing diagnosis of pseudoarthrosis based on the failure strain of bone, measurement error, and retrospective data. These steps include obtaining high-quality flexion-extension studies, the application of proposed diagnostic thresholds, and the use of image stabilization for conclusive diagnosis, when motion is near thresholds. The necessity for an accurate diagnosis with minimal radiation exposure underscores the need for further optimization and standardization in diagnosing pseudoarthrosis following ACDF surgery. CLINICAL SIGNIFICANCE: In a symptomatic postspine fusion patient, it is important to diagnose or rule-out pseudoarthrosis. There are currently no well-validated diagnostic tests for this condition. Incorporating strain-based intervertebral motion analysis into the diagnosis could lead to a standardized and validated test for detecting spine pseudoarthrosis.

Computer Assisted Navigation Does Not Improve Outcomes in Posterior Fusion for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The aim of this study was to compare the efficacy of CT-based computer assisted navigation (CAN) to conventional pedicle screw placement for patients with Adolescent Idiopathic Scoliosis (AIS). METHODS: This retrospective cohort study drew data from the National Readmissions Database, years 2016-2019. Patients undergoing posterior fusion for AIS, either via CAN or fluoroscopic-guided procedures, were identified via ICD-10 codes. Multivariate regression was performed to compare outcomes between operative techniques. Negative binomial regression was used to asses discharge disposition, while Gamma regression was performed to assess length of stay (LOS) and total charges. Patient demographics and comorbidities, measured via the Elixhauser comorbidity index, were both controlled for in our regression analysis. RESULTS: 28,868 patients, 2095 (7.3%) undergoing a CAN procedure, were included in our analysis. Patients undergoing CAN procedures had increased surgical complications (Odds Ratio (OR) 2.23; P < 0.001), namely, blood transfusions (OR 2.47; P < 0.001). Discharge disposition and LOS were similar, as were reoperation and readmission rates; however, total charges were significantly greater in the CAN group (OR 1.37; P < 0.001). Mean charges were 191,489.42 (119,302.30) USD for conventional surgery vs 268 589.86 (105,636.78) USD for the CAN cohort. CONCLUSION: CAN in posterior fusion for AIS does not appear to decrease postoperative complications and is associated with an increased need for blood transfusions. Given the much higher total cost of care that was also seen with CAN, this study calls into question whether the use of CAN is justified in this setting.

Navigating the complexity of spinal cord injuries with retained foreign bodies and the diagnostic challenge of lead toxicity-a case reportaaa.

INTRODUCTION: Retained shrapnel from gunshots is a common occurrence; however, retained shrapnel within the spinal canal is exceedingly uncommon. Guidelines for removal and treatment of these cases are a difficult topic, as surgical removal is not necessarily without consequence, and retention can lead to possible further injury or a secondary disease process of plumbism, which can be difficult to diagnose in this population. CASE PRESENTATION: This case report provides a unique example of a young patient with retained shrapnel from a gunshot. This patient suffered an initial spinal cord injury due to a gunshot and secondarily presented with abdominal pain, fatigue, elevated blood lead levels, and was diagnosed with plumbism. This was addressed with operative removal of shrapnel and posterior instrumented spinal fusion, resulting in decreased lead levels and symptom resolution postoperatively. DISCUSSION: Lead toxicity risk in patients with retained shrapnel, particularly in the spine, warrants vigilant monitoring. While management guidelines lack consensus, symptomatic lead toxicity may necessitate intervention. Residual neurological deficits complicate evaluation, emphasizing individualized management decisions.

A Geometrical Explanation for Change in Pelvic Tilt (or Lack of Change) Following Long Spinal Fusions.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: Examine the relationship between compensatory pelvic retroversion, positive sagittal imbalance (measured by C2 tilt), and the C2 pelvic angle (C2PA) in patients before long spinal fusions; and to determine the association between changes in C2PA and pelvic tilt (PT) following long spinal fusions. BACKGROUND: Adult spinal deformity surgical goals often include a PT target, yet patients frequently demonstrate persistent compensatory pelvic retroversion following surgery. METHODS: Adults above 18 years old undergoing long spinal fusions (>4 levels) with standing preoperative and postoperative radiographs were included. To examine drivers of preoperative sagittal balance, regression models were fit to estimate the association between preoperative C2PA and pelvic incidence with preoperative PT and C2 tilt. To predict postoperative change in PT, multivariable regression was used to estimate change in PT, adjusting for change in C2PA and preoperative C2 tilt. RESULTS: Among the 80 patients identified, the median age was 61 (IQR: 45-72) and 46 (58%) were female. The median number of levels fused was 10 (IQR: 8-13) and 55 (69%) were instrumented to the sacrum/pelvis. Preoperative C2PA had a significant nonlinear association with preoperative PT ( r2 =0.81, P <0.001) and preoperative C2 tilt ( r2 =0.41, P =0.002). Postoperative change in PT was strongly associated with change in C2PA (ß=0.81; P <0.001) and preoperative C2 tilt (ß=0.55; P <0.001). CONCLUSIONS: Following long spinal fusions, change in PT (or lack thereof) can be reliably predicted based on change in C2PA and preoperative C2 tilt. In patients with normal preoperative C2 tilt, the change in C2PA is nearly equivalent to the change in PT, but in patients with more positive C2 tilt (sagittal imbalance), a greater change in C2PA will be required to achieve an equivalent change in PT. LEVEL OF EVIDENCE: 3.

Preoperative Dehydration Predicts Adverse Events Following Anterior Cervical Discectomy and Fusion.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a common procedure for neck arthritis, typically alleviating pain and improving function. Preoperative dehydration has been correlated with postoperative infection, acute renal failure, deep vein thrombosis, and increased hospital length of stay. However, some studies have suggested that preoperative dehydration has a minimal relationship with postoperative outcomes, specifically in arthroplasty and lumbar surgery candidates. METHODS: Patients who underwent ACDF from 2015 to 2020 as part of the American College of Surgeons National Surgical Quality Improvement Program database were identified. We excluded patients who presented with acute trauma. Dehydration was determined using the accepted definition of preoperative blood urea nitrogen to creatinine ratio greater than 20. Lengths of stay and 30-day postoperative adverse events were compared between dehydrated and nondehydrated cohorts, adjusting for baseline features using standard multivariate regression. RESULTS: We identified 14,932 patients, and 4206 (28.1%) of whom were preoperatively dehydrated. Dehydrated patients had significantly higher odds of wound, hematological, and pulmonary complications; Clavien-Dindo grade IV, delayed length of stay (>5 days); and a lower likelihood of being discharged home (P < 0.005), even after controlling for demographic features (eg, sex, age, body mass index, race, and ethnicity). Furthermore, linear regression suggested an overall half-day increased length of hospital stay for dehydrated patients (95% CI [0.36, 0.60], P < 0.001). CONCLUSION: Preoperative dehydration is common among ACDF surgery patients and appears to correlate with an increased risk of postoperative complications and prolonged length of hospital stay. Evaluation of a patient's hydration status from standard preoperative laboratory metrics can be employed for risk stratification, patient counseling, and timing of ACDF surgeries.

Vascular Injury After Scoliosis Correction in Ehlers-Danlos Syndrome: Proceed With Caution.

Ehlers-Danlos syndrome (EDS) is a rare inherited connective tissue disorder characterized by collagen synthesis disruption, resulting in joint hyperlaxity, skin and vascular fragility, and bleeding diathesis. Patients with EDS are susceptible to spinal deformities, with scoliosis accounting for up to 23.4% of musculoskeletal abnormalities. Conservative management is often trialed initially; however, severe scoliosis can lead to significant sagittal imbalance and cardiopulmonary compromise. Surgical intervention for scoliosis correction in patients with EDS presents unique challenges because of tissue fragility and an increased risk of vascular and wound complications. This case report discusses a 20-year-old man with type II EDS and scoliosis, who experienced retroperitoneal compartment syndrome, significant left lower extremity weakness, and loss of sensation after scoliosis correction surgery. The report also provides an overview of the existing literature on scoliosis surgery outcomes in patients with EDS, highlighting the need for heightened vigilance and cautious surgical approaches.

The articular surface technique for lumbar pedicle screw placement: a 3D feasibility study.

Background: Traditional pedicle screws (TPSs) and cortical based trajectory pedicle screws each apply stability with fusions of the lumbar spine and have shown good success. However, the technical considerations of each technique imply complications of loosening and failure that either technique is uniquely prone to having. The current study proposes a new pedicle screw technique through the articular surface of the vertebral superior facet. It is hypothesized that this path will allow utilization of a larger screw that rivals that of the TPS technique, while also maintaining the high-density bone encountered in the cortical based trajectory technique. Methods: Retrospective review of 50 consecutive trauma patients that underwent lumbar computed tomography (CT) scans at a Level 1 Trauma Center in the age range 18-45. These scans were uploaded to Brainlab software for ideal starting point and trajectory mapping of pedicle screws coursing through each superior facet and pedicle of vertebral levels L1-S1 without cortical breach. Satisfactory pedicle screw variables consisted of a medial angle <10 degrees, screw length at least 30 mm, screw width at least 5.0 mm, and starting point measurements such as distance to the inferior articular surface and distance to the lateral articular surface. Results: A total of 600 virtual pedicle screws were placed, in which 525 were satisfactory and measured with the above variables. The pedicle widths were shown to significantly widen with lower-level vertebra in the lumbar spine. Approximately 72% of unsuccessful pedicle screws were placed in levels L1 and L2 allowing wider pedicle screws to be placed more further down the vertebral column. Conclusions: The articular surface technique (AST) for pedicle screw placement is a viable alternative in lumbar spinal fusions that offers decreased soft tissue dissection. However, the technique is likely better suited for lower lumbar fusions in L3 to S1.

The 8-item Modified Frailty Index Is an Effective Risk Assessment Tool in Anterior Cervical Decompression and Fusion.

STUDY DESIGN: Case-control study; Level of evidence, 3. OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is one of the most common procedures for cervical diseases often with reliable outcomes. However, morbidity rates can be as high as 19.3% so appropriate patient selection and risk stratification is imperative. Our modified frailty index (MFI) predicts postoperative complications after other orthopaedic procedures. We hypothesized that this index would predict complications in a large cohort of ACDF patients. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, including patients who underwent ACDF from 2015-2020. An 8-item MFI score was calculated for each patient. We recorded 30-days postoperative complications, readmission, and reoperation rates, adjusting for baseline features using standard multivariate regression. This project was approved of by the University of Texas Health Science Center Institutional Review Board and an IRB exception was granted. RESULTS: We identified 17 662 ACDF cases. Patients with MFI of 5 or greater had a 37.53 times increased odds of incurring postoperative complications compared to patients with MFI of 0 (P < .001) even when age, sex, race, and ethnicity were controlled for. Specifically, life-threatening Clavien-Dindo IV complications, as well as wound, cardiac, renal, and pulmonary complications were significantly increased in patients with an MFI of 5 or greater. Also, as MFI increased from 1-2 to 3-4 to 5 or greater, the odds of readmission increased from 1.36 to 2.31 to 5.42 times (P < .001) and odds of reoperation from 1.19 (P = .185) to 2.3 to 6.54 times (P < .001). Frailty was still associated with increased complications, readmission, and reoperation after controlling for demographic data, including age, as well as operative time and length of stay. CONCLUSION: Frailty is highly predictive of postoperative complications, readmission, and reoperation following ACDF. Employing a simple frailty evaluation can guide surgical decision-making and patient counseling for cervical disease.

Survival rates in atlanto-occipital dissociation: a look at the past 20 years.

BACKGROUND CONTEXT: Atlanto-occipital dissociation (AOD) has historically been considered a fatal injury. Recent small case series, however, have suggested that AOD injuries have become increasingly survivable. There has not been an adequately powered study that confirms this. PURPOSE: The aim of this study is to assess whether the survival rate for patients with AOD increased over time. STUDY DESIGN/SETTING: Retrospective case series. PATIENT SAMPLE: Patients with traumatic AOD identified from our Level 1 Trauma Center database. OUTCOME MEASURES: Mortality following traumatic AOD. METHODS: Patients with traumatic AOD from 1996 to 2019 were retrospectively identified from our Level 1 Trauma Center database using International Classification of Diseases 9 and 10 codes. Patients were stratified into two cohorts- those diagnosed before August 1, 2015 and after. RESULTS: A total of 52 patients met our inclusion criteria and were analyzed. Mean age was 34.41 (11.71), with 34 (65.4) females, and 26 (50) Hispanics. Mean BMI was 28.13 (7.30), mean injury severity score was 40.79 (21.72), and mean Glasgow coma scale was 5.91 (4.72). Overall, 33 patients died (63.5%). The mortality rate before 2015 was 81.80%, this number dropped down to 50% for those who were treated post 2015 (p=.01). CONCLUSIONS: This study demonstrates that patients treated recently for AOD at a level 1 trauma center were more likely to survive than patients treated in the past at the same center. Possible reasons for the improved survival rate seen in this study include: increased awareness of AOD, improved diagnostic protocols with more uniform computed tomography based imaging, and advances in the care of these patients.

Opportunistic application of phantom-less calibration methods for fracture risk prediction using QCT/FEA.

OBJECTIVES: Quantitative computed tomography (QCT)-based finite element analysis (FEA) implements a calibration phantom to estimate bone mineral density (BMD) and assign material properties to the models. The objectives of this study were to (1) propose robust phantom-less calibration methods, using subject-specific tissues, to obtain vertebral fracture properties estimations using QCT/FEA; and (2) correlate QCT/FEA predictions to DXA values of areal BMD. METHODS: Eighty of a cohort of 111 clinical QCT scans were used to obtain subject-specific parameters using a phantom calibration approach and for the development of the phantom-less calibration equations. Equations were developed based on the HU measured from various soft tissues and regions, and using multiple linear regression analyses. Thirty-one additional QCT scans were used for cross-validation of QCT/FEA estimated fracture loads from the L3 vertebrae based on the phantom and phantom-less equations. Finally, QCT/FEA-predicted fracture loads were correlated with aBMD obtained from DXA. RESULTS: Overall, 217 QCT/FEA models from 31 subjects (20 females, 11 men) with mean ages of 69.6 (13.1) and 67.3 (14) were used to cross-validate the phantom-less equations and assess bone strength. The proposed phantom-less equations showed high correlations with phantom-based estimates of BMD (99%). Cross-validation of QCT/FEA-predicted fracture loads from phantom-less equations and phantom-specific outcomes resulted in high correlations for all proposed methods (0.94-0.99). QCT/FEA correlation outcomes from the phantom-less equations and DXA-aBMD were moderately high (0.64-0.68). CONCLUSIONS: The proposed QCT/FEA subject-specific phantom-less calibration methods demonstrated the potential to be applied to both prospective and retrospective applications in the clinical setting. KEY POINTS: • QCT/FEA overcomes the disadvantages of DXA and improves fracture properties predictions of vertebrae. • QCT/FEA fracture estimates using the phantom-less approach highly correlated to values obtained using a calibration phantom. • QCT/FEA prediction using a phantom-less approach is an accurate alternative over phantom-based methods.

Dual-energy estimates of volumetric bone mineral densities in the lumbar spine using quantitative computed tomography better correlate with fracture properties when compared to single-energy BMD outcomes.

It is estimated that over 200 million people worldwide are affected by osteoporosis. Vertebral fracture risk prediction using dual energy x-ray absorptiometry (DXA) is confounded by limitations of the technology, such as 2D measurements of bone mineral density (BMD), inability to measure bone distribution and heterogeneity, and potential overestimations of BMD due to degenerative diseases. To overcome these shortcomings, single energy (SE) quantitative computed tomography (QCT) imaging estimates of Hounsfield units (HU) and volumetric BMD have been implemented as alternative methodologies for assessing fracture risk. However, marrow fat within the vertebrae can highly affect the vBMD and fracture properties estimations. To address this issue, 54 vertebrae were dissected from nine cadaveric spines and scanned using SE-QCT (120kVp) and dual energy (DE)-QCT (80/140 kVp), with the latter accounting for marrow fat within the vertebrae. The vertebrae were then scanned using DXA and subjected to mechanical testing to obtain fracture properties. aBMD outcomes from DXA showed a better correlation with DE-QCT vBMD versus SE outcomes [DE: aBMD vs. vBMD (R2: 0.61); SE: aBMD vs. vBMD (R2: 0.27)]. SE-QCT underestimated vertebral vBMD by -56% (p<0.0001) when compared to DE-QCT. vBMD estimates from SE-QCT could predict 45% and 37% of the vertebral failure loads and stiffness, respectively, compared to 67% and 46% from DE-QCT. DE-QCT vBMD outcomes highly correlated with fracture properties of vertebrae as compared to SE-QCT metrics. As DE scanning has the ability to correct for the effects of bone marrow fat, estimated vBMD from SE-QCT were significantly underestimated compared to DE-QCT. Dual energy CT scanning has the potential to more accurately predict vertebral failure and aid the clinician in the evaluation of appropriate interventions. Future studies should consider implementing DE-QCT in their fracture assessment.

Obesity and calcification of the ligaments of the spine: a comprehensive CT analysis of the entire spine in a random trauma population.

BACKGROUND CONTEXT: Obesity, which is currently surging to epidemic levels within the United States, has been linked to hyperostotic conditions like diffuse idiopathic skeletal hyperostosis (DISH) and ossification of the posterior longitudinal ligament (OPLL). Excess adipose tissue and insulin-resistance may cause a systemic increase in serum levels of proinflammatory cytokines and these signals can affect bone metabolism. Spinal ligaments and discs may have receptors for these signaling molecules. Anecdotal observations at this institution suggested that there is a clinically important subset of younger patients with obesity and multilevel stenosis in the presence of unusual calcification of the spinal ligaments that is distinct from DISH. PURPOSE: To determine if there is an association between truncal obesity and calcifications of the spine in nonelderly adults. STUDY DESIGN/SETTING: This is a retrospective analysis of 214 sequential trauma patients between the ages of 29 and 50. Patients' age, sex, truncal obesity, history of hypertension, and diabetes were assessed for association with ligamentous calcification of the spine. PATIENT SAMPLE: Sequential trauma patients were chosen from our institution's trauma database between 2006 and 2007. METHODS: Full spine computed tomography (CT) imaging was examined for bone formation in the region of the anterior longitudinal ligament (ALL) and annulus, posterior longitudinal ligament (PLL) and annulus, and the ligamentum flavum (LF). Visceral and subcutaneous abdominal fat were also evaluated. The authors report no study funding sources or conflicts of interest. OUTCOME MEASURES: Calcification of the ALL, PLL, and LF were assigned a score at each level and then combined for a total calcification score (TCS) for the entire spine. Obesity was estimated using a truncal body mass index (TBMI) by using a previously validated CT derived truncal total adiposity volume (TAV). RESULTS: ALL calcification was associated with age, male gender, hypertension, and increased adiposity. PLL calcification was significantly associated with age and hypertension. LF calcification was only associated with increased obesity. CONCLUSIONS: In our analysis of nonelderly patients, LF calcification was independently associated with truncal obesity. This implies obesity plays a greater role in calcification than could be accounted for by simply age-related degeneration or gender.

Anterior Fixation of Floating Facet Fractures in the Cervical Spine: A Prospective Case Series and Biomechanical Analysis.

BACKGROUND: Unilateral fractures involving complete separation of the lateral mass from the vertebra and lamina (floating lateral mass fractures) are a unique subset of cervical spine fractures. These injuries are at significant risk for displacement without operative fixation. Posterior fixation has proven to facilitate adequate fusion. However, there are few data supporting the clinical success of single-level anterior fixation. METHODS: Biomechanical evaluation of floating lateral mass fractures and a consecutive case series of patients with rotationally unstable floating lateral mass fractures treated with anterior fixation using an integrated cage-screw device with anterior plating (ICSD) was performed. The study comprised 7 fresh human cadaver cervical spines (C2-C7), and 11 patients with floating lateral mass fractures. Segmental flexibility testing evaluating axial rotation, flexion/extension, and lateral bending was performed in a cadaveric model after 2 types of single-level anterior fixation and 1 type of 2-level posterior fixation. Eleven patients with a floating lateral mass fracture of the cervical spine underwent anterior fixation with an ICSD. Radiographs and clinical outcomes were retrospectively reviewed. RESULTS: Compared with the intact condition, posterior instrumentation significantly (P < .05) reduced range of motion (ROM) in all 3 planes; anterior fixation with cervical plate and interbody spacer significantly reduced ROM in lateral bending only; and the ICSD significantly reduced ROM in flexion/extension and lateral bending. In the clinical arm, there were no long-term complications, subsidence >2 mm, failure of fixation, reoperation, pseudoarthrosis, or listhesis at final follow-up. CONCLUSIONS: The addition of 2 screws placed through a cervical cage can improve anterior fixation in a human cadaveric model of floating lateral mass fractures. Early clinical results demonstrate a low complication rate and a high rate of healing with single-level anterior fixation using this technique.

How stem cell composition in bone marrow aspirate relates to clinical outcomes when used for cervical spine fusion.

Anterior cervical discectomy and fusion (ACDF) is performed to relieve pain caused by degenerative disk disease and nerve obstruction. As an alternative to bone graft, autologous concentrated bone marrow aspirate (CBMA) is used to achieve vertebral fusion with a satisfactory success rate. This has been attributed in part to bone marrow-resident mesenchymal stromal cells (MSCs) with the capacity to differentiate into osteoblasts and generate bone tissue. To date, there has been no study comparing cellular yields, MSC frequencies and their osteogenic potential with ACDF outcome. Patients (n = 24) received ACDF with CBMA and allograft bone matrix. Colony forming unit fibroblast (CFU-F) and CFU-osteoblasts (CFU-O) assays were performed on CBMA samples to enumerate MSCs (CFU-F) and osteogenic MSCs (CFU-O). CFUs were normalized to CBMA volume to define yield and also to mononuclear cells (MNC) to define frequency. After 1-year, fusion rates were good (86.7%) with pain and disability improved. There was a negative relationship between MNC and CFU-F measurements with age of patient and CFU-Os negatively correlated with age in females but not males. Tobacco use did not affect CBMA but was associated with poorer clinical outcome. Surprisingly, we found that while high-grade fusion was not associated with CFU-O, it correlated strongly (p<0.0067) with CBMA containing the lowest frequencies of CFU-F (3.0x10(-6)-5.83x10(-5) CFU-F/MNC). MNC levels alone were not responsible for the results. These observations suggest that osteogenesis by human bone marrow is controlled by homeostatic ratio of MSCs to other cellular bone marrow components rather than absolute level of osteogenic MSCs, and that a lower ratio of MSCs to other cellular components in marrow tends to predict effective osteogenesis during ACDF. The results presented herein challenge the current dogma surrounding the proposed mechanism of MSCs in bone healing.

Rapid Osteogenic Enhancement of Stem Cells in Human Bone Marrow Using a Glycogen-Synthease-Kinase-3-Beta Inhibitor Improves Osteogenic Efficacy In Vitro and In Vivo.

Non-union defects of bone are a major problem in orthopedics, especially for patients with a low healing capacity. Fixation devices and osteoconductive materials are used to provide a stable environment for osteogenesis and an osteogenic component such as autologous human bone marrow (hBM) is then used, but robust bone formation is contingent on the healing capacity of the patients. A safe and rapid procedure for improvement of the osteoanabolic properties of hBM is, therefore, sought after in the field of orthopedics, especially if it can be performed within the temporal limitations of the surgical procedure, with minimal manipulation, and at point-of-care. One way to achieve this goal is to stimulate canonical Wingless (cWnt) signaling in bone marrow-resident human mesenchymal stem cells (hMSCs), the presumptive precursors of osteoblasts in bone marrow. Herein, we report that the effects of cWnt stimulation can be achieved by transient (1-2 hours) exposure of osteoprogenitors to the GSK3ß-inhibitor (2'Z,3'E)-6-bromoindirubin-3'-oxime (BIO) at a concentration of 800 nM. Very-rapid-exposure-to-BIO (VRE-BIO) on either hMSCs or whole hBM resulted in the long-term establishment of an osteogenic phenotype associated with accelerated alkaline phosphatase activity and enhanced transcription of the master regulator of osteogenesis, Runx2. When VRE-BIO treated hBM was tested in a rat spinal fusion model, VRE-BIO caused the formation of a denser, stiffer, fusion mass as compared with vehicle treated hBM. Collectively, these data indicate that the VRE-BIO procedure may represent a rapid, safe, and point-of-care strategy for the osteogenic enhancement of autologous hBM for use in clinical orthopedic procedures. Stem Cells Translational Medicine 2018;7:342-353.

Rate of contralateral hip fracture after dynamic hip screw vs intramedullary nail for treatment of pertrochanteric hip fractures.

A retrospective, comparative study was performed reviewing the electronic medical records and digital radiographs of patients who underwent treatment for intertrochanteric and pertrochanteric hip fractures with either a hip screw and side plate (HSSP) or intramedullary nail. A total of 430 patients were treated with HSSP, and 725 were managed with a cephalomedullary nail (CMN). Of these, 103 sustained a contralateral hip fracture. Fixation technique was not associated with a significant difference in the rate of contralateral fracture. Among the patients with a contralateral fracture, the median time to contralateral fracture was 119.28 months following HSSP and 81.97 months following CMN. Bisphosphonate use was found to be a significant predictor of contralateral fracture for all patients, but when matching using propensity scores, its use was found to be insignificant. In conclusion, there was no difference in the rate of subsequent contralateral hip fracture when comparing HSSP with CMN. Additionally, the time to second surgery between the two treatment modalities was found to be statistically insignificant. It is unclear if bisphosphonate use increased the odds of having a contralateral fracture, regardless of the surgical intervention. The difference in the bisphosphonate effect using propensity score matching suggests that the results may be due to confounding variables and bias.

An allograft generated from adult stem cells and their secreted products efficiently fuses vertebrae in immunocompromised athymic rats and inhibits local immune responses.

BACKGROUND CONTEXT: Spine pain and the disability associated with it are epidemic in the United States. According to the National Center for Health Statistics, more than 650,000 spinal fusion surgeries are performed annually in the United States, and yet there is a failure rate of 15%-40% when standard methods employing current commercial bone substitutes are used. Autologous bone graft is the gold standard in terms of fusion success, but the morbidity associated with the procedure and the limitations in the availability of sufficient material have limited its use in the majority of cases. A freely available and immunologically compatible bone mimetic with the properties of live tissue is likely to substantially improve the outcome of spine fusion procedures without the disadvantages of autologous bone graft. PURPOSE: This study aimed to compare a live human bone tissue analog with autologous bone grafting in an immunocompromised rat model of posterolateral fusion. DESIGN/SETTING: This is an in vitro and in vivo preclinical study of a novel human stem cell-derived construct for efficacy in posterolateral lumbar spine fusion. METHODS: Osteogenically enhanced human mesenchymal stem cells (OEhMSCs) were generated by exposure to conditions that activate the early stages of osteogenesis. Immunologic characteristics of OEhMSCs were evaluated in vitro. The secreted extracellular matrix from OEhMSCs was deposited on a clinical-grade gelatin sponge, resulting in bioconditioned gelatin sponge (BGS). Bioconditioned gelatin sponge was used alone, with live OEhMSCs (BGS+OEhMSCs), or with whole human bone marrow (BGS+hBM). Efficacy for spine fusion was determined by an institutionally approved animal model using 53 nude rats. RESULTS: Bioconditioned gelatin sponge with live OEhMSCs did not cause cytotoxicity when incubated with immunologically mismatched lymphocytes, and OEhMSCs inhibited lymphocyte expansion in mixed lymphocyte assays. Bioconditioned gelatin sponge with live OEhMSC and BGS+hBM constructs induced profound bone growth at fusion sites in vivo, with a comparable rate of fusion with syngeneic bone graft (negative [0 of 10], BGS alone [0 of 10], bone graft [7 of 10], BGS+OEhMSC [10 of 15], and BGS+hBM [8 of 8]). CONCLUSIONS: Collectively, these studies demonstrate that BGS+OEhMSC constructs possess low immunogenicity and drive vertebral fusion with efficiency matching syngeneic bone graft in rodents. We also demonstrate that BGS serves as a promising scaffold for spine fusion when combined with hBM.

Optimization of Scaffolds and Surface-Based Treatments for Orthopedic Applications.

Improving spinal fusion by optimizing scaffold and surface engineering is a topic of interest for both surgeons and researchers. Concerns regarding patient safety with off-label use of bone morphogenetic protein (BMP) have increased, and patients are choosing minimally invasive spine surgery to lessen morbidity by avoiding harvest of bone graft. These trends may be driving studies on how surgeons can avoid issues associated with biologics (e.g., cost, morbidity), while achieving efficacious and safe bone fusion.

The Relationship of Obesity to Increasing Health-Care Burden in the Setting of Orthopaedic Polytrauma.

BACKGROUND: With the rise of obesity in the American population, there has been a proportionate increase of obesity in the trauma population. The purpose of this study was to use a computed tomography-based measurement of adiposity to determine if obesity is associated with an increased burden to the health-care system in patients with orthopaedic polytrauma. METHODS: A prospective comprehensive trauma database at a level-I trauma center was utilized to identify 301 patients with polytrauma who had orthopaedic injuries and intensive care unit admission from 2006 to 2011. Routine thoracoabdominal computed tomographic scans allowed for measurement of the truncal adiposity volume. The truncal three-dimensional reconstruction body mass index was calculated from the computed tomography-based volumes based on a previously validated algorithm. A truncal three-dimensional reconstruction body mass index of <30 kg/m(2) denoted non-obese patients and ≥ 30 kg/m(2) denoted obese patients. The need for orthopaedic surgical procedure, in-hospital mortality, length of stay, hospital charges, and discharge disposition were compared between the two groups. RESULTS: Of the 301 patients, 21.6% were classified as obese (truncal three-dimensional reconstruction body mass index of ≥ 30 kg/m(2)). Higher truncal three-dimensional reconstruction body mass index was associated with longer hospital length of stay (p = 0.02), more days spent in the intensive care unit (p = 0.03), more frequent discharge to a long-term care facility (p < 0.0002), higher rate of orthopaedic surgical intervention (p < 0.01), and increased total hospital charges (p < 0.001). CONCLUSIONS: Computed tomographic scans, routinely obtained at the time of admission, can be utilized to calculate truncal adiposity and to investigate the impact of obesity on patients with polytrauma. Obese patients were found to have higher total hospital charges, longer hospital stays, discharge to a continuing-care facility, and a higher rate of orthopaedic surgical intervention.