Elder, Benjamin D.

Abstract BACKGROUND Low bone mineral density (BMD) on dual energy x-ray absorptiometry (DXA) is likely a risk factor for proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). However, prior instrumentation and degenerative changes can preclude a lumbar BMD measurement. Hounsfield units (HU) represent an alternative method to estimate BMD via targeted measurements at the intended operative levels. OBJECTIVE To determine if patients with lower HU at the upper instrumented vertebrae (UIV) and vertebral body superior to the UIV (UIV + 1) are at greater risk for PJK and PJF. METHODS A retrospective chart review identified patients at least 50 yr of age who underwent instrumented lumbar fusion with pelvic fixation, a UIV from T10 to L2, and a preoperative computed tomography (CT) encompassing the UIV. HU were measured at the UIV, UIV + 1, and the L3-L4 vertebral bodies. RESULTS A total of 150 patients (80 women and 70 men) were included with an average age of 66 yr and average follow-up of 32 mo. Multivariable logistic regression analysis with an area under the curve (AUC) of 0.89 demonstrated HU at the UIV/UIV + 1 as the only independent predictor of PJK/PJF with an odds ratio of 0.94 ( P -value = .031) for a change in a single HU. Patients with HU at UIV/UIV + 1 of <110 (n = 35), 110 to 160 (n = 73), and >160 (n = 42) had a rate of PJK/PJF of 63%, 27%, and 12%, respectively ( P -value < .001). CONCLUSION Patients with lower HU at the UIV and UIV + 1 were significantly associated with PJK and PJF, with an optimal cutoff of 122 HU that maximizes sensitivity and specificity.

AbstractAlthough bone marrow‐derived mesenchymal stem cells (BMCs) have been widely used in spinal fusion procedures, adipose‐derived stem cells (ASCs) offer a number of advantages as an alternative clinical cell source. This study directly compares the efficacy of ASCs and BMCs from the same donor animals to achieve successful fusion when combined with a clinical‐grade bone graft substitute in a rat lumbar fusion model. ASCs and BMCs were isolated from the same Lewis donor rats and grown to passage 2 (P2). Single‐level bilateral posterolateral intertransverse process lumbar fusion surgery was performed on syngeneic rats divided into three experimental groups: clinical‐grade bone graft substitute alone (CBGS); CBGS+ rat ASCs (rASC); and, CBGS+ rat BMCs (rBMC). Eight weeks postoperatively, fusion was evaluated via micro‐CT, manual palpation and histology. In vitro analysis of the osteogenic capacity of rBMCs and rASCs was also performed. Results indicated that the average fusion volume in the rASC group was the largest and was significantly larger than the CBGS group. Although the rASC group displayed the highest fusion rates via micro‐CT and manual palpation, this difference was not statistically significant. Cell‐seeded grafts showed more histological bone formation than cell‐free grafts. P2 rASCs and rBMCs displayed similar in vitro osteogenic differentiation capacities. Overall, this study showed that, when combined with a clinical‐grade bone graft substitute in a rat model, rASCs cells yielded the largest fusion masses and comparable fusion results to rBMCs. These results add to growing evidence that ASCs provide an attractive alternative to BMCs for spinal fusion procedures.

Study Design: This was a retrospective chart review. Objective: The objective of this study was to compare the effect of teriparatide on Hounsfield Units (HU) in the cervical spine, thoracic spine, lumbar spine, sacrum, and pelvis. Second, to correlate HU changes at each spinal level with bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA). Summary of Background Data: HU represent a method to estimate BMD and can be used either separately or in conjunction with BMD from DXA. Materials and Methods: A retrospective chart review included patients who had been treated with at least 6 months of teriparatide. HU were measured in the vertebral bodies of the cervical, thoracic, and lumbosacral spine and iliac crests. Lumbar and femoral neck BMD as measured on DXA was collected when available. Results: One hundred twenty-five patients were identified for analysis with an average age of 67 years who underwent a mean (±SD) of 22±8 months of teriparatide therapy. HU improvement in the cervical spine was 11% (P=0.19), 25% in the thoracic spine (P=0.002), 23% in the lumbar spine (P=0.027), 17% in the sacrum (P=0.11), and 29% in the iliac crests (P=0.09). Lumbar HU correlated better than cervical HU with BMD as measured on DXA. Conclusions: Teriparatide increased average HU in the thoracolumbar spine to a proportionally greater extent than the cervical spine. The cervical spine had a higher baseline starting HU than the thoracolumbar spine. Lumbar HU correlated better than cervical and thoracic HU with BMD as measured on DXA.

OBJECTIVE The use of intrawound vancomycin powder in spine surgery has been shown to decrease the rate of surgical site infections; however, the optimal dose is unknown. High-dose vancomycin inhibits osteoblast proliferation in vitro and may decrease the rate of solid arthrodesis. Bone marrow–derived mesenchymal stem cells (BMSCs) are multipotent cells that are a source of osteogenesis in spine fusions. The purpose of this study was to determine the effects of vancomycin on rat BMSC viability and differentiation in vitro. METHODS BMSCs were isolated from the femurs of immature female rats, cultured, and then split into two equal groups; half were treated to stimulate osteoblastic differentiation and half were not. Osteogenesis was stimulated by the addition of 50 µg/mL l-ascorbic acid, 10 mM β-glycerol phosphate, and 0.1 µM dexamethasone. Vancomycin was added to cell culture medium at concentrations of 0, 0.04, 0.4, or 4 mg/mL. Early differentiation was determined by alkaline phosphatase activity (4 days posttreatment) and late differentiation by alizarin red staining for mineralization (9 days posttreatment). Cell viability was determined at both the early and late time points by measurement of formazan colorimetric product. RESULTS Viability within the first 4 days decreased with high-dose vancomycin treatment, with cells receiving 4 mg/mL vancomycin having 40%–60% viability compared to the control. A gradual decrease in alizarin red staining and nodule formation was observed with increasing vancomycin doses. In the presence of the osteogenic factors, vancomycin did not have deleterious effects on alkaline phosphatase activity, whereas a trend toward reduced activity was seen in the absence of osteogenic factors when compared to osteogenically treated cells. CONCLUSIONS Vancomycin reduced BMSC viability and impaired late osteogenic differentiation with high-dose treatment. Therefore, the inhibitory effects of high-dose vancomycin on spinal fusion may result from both reduced BMSC viability and some impairment of osteogenic differentiation.

Abstract Background: The relationship of the area of the aqueduct on quantification of the aqueductal stroke volume (SV) and max velocity need further investigation. Our aim was to assess the influence of the area of the aqueduct on quantification of the aqueductal SV and max velocity measured with phase contrast magnetic resonance imaging (PC-MRI) within the cerebral aqueduct at the level of the intercollicular sulcus.Materials and Methods: Nine healthy volunteers (mean age 29.6 yrs) were enrolled in the study and brain MRIs were performed on a 3.0T system. Quantitative analysis of aqueductal cerebrospinal fluid (CSF) flow was performed using manual regions of interest (ROI) placement. ROIs were separately drawn for each of 12 phases of the cardiac cycle, and changes in aqueduct size during the cardiac cycle were determined. Stroke volumes were calculated uses the first and ninth aqueductal ROIs and compared to each other. Max velocities at the 12 phases were also collected, and the relationship between the area and max velocity and the impact on SV were analyzed.Results: There was variation in the size of the aqueduct during the cardiac cycle, the first area（S1）was larger than the ninth（S9）. The first max velocity（Vmax1）was less than the ninth（Vmax9）. Additionally, there was a significant different between the stroke volume calculated using the first aqueductal ROI (SV1) and the ninth（SV9）. Conclusions: There is variation in the size of the cerebral aqueduct which is used to calculate stroke volume and other CSF flow parameters during the cardiac cycle. The maximum velocity may be inversely proportional to the area of ​​the aqueduct. In order to establish reliable reference values for CSF flow parameters in future studies, a variable ROI, to account for cardiac cycle variation, should be considered and incorporated.

Study Design: Retrospective cohort study. Objective: Studies investigating the impact of interbody subsidence in ACDF suggest a correlation between subsidence and worse radiographic and patient-reported outcomes. The purpose of this study was to assess whether allograft subsidence assessed on CT is associated with worse cervical alignment. Methods: We performed a retrospective review of a prospective cohort of patients undergoing 1 to 3 level ACDF. Cervical alignment was assessed on standing radiographs performed preoperatively, less than 2 months postoperatively, and greater than 6 months postoperatively. Allograft subsidence was assessed on CT scan performed at least 6 months postoperatively. Patients with at least 1 level demonstrating greater than 4mm of cage subsidence were classified as severe subsidence. Student’s t-test was used to compare all means between groups. Results: We identified 66 patients for inclusion, including 56 patients with non-severe subsidence and 10 patients with severe subsidence. For the entire cohort, there was a significant increase in C2-7 Lordosis (p = 0.005) and Segmental Lordosis (p < 0.00 001) from preoperative to early postoperative. On comparison of severely and non-severely subsided levels, severely subsided levels demonstrated a significantly greater loss of segmental lordosis from early to mid-term follow-up than non-severely subsided levels (-4.89 versus -2.59 degrees, p < 0.0001), manifesting as a significantly lower segmental lordosis at >6 months postoperative (0.54 versus 3.82 degrees, p < 0.00 001). There were no significant differences in global cervical alignment parameters between patients with severe and non-severe subsidence. Conclusions: Severe subsidence is associated with a significant increase in loss of segmental lordosis, but has minimal effect on global cervical alignment parameters.

OBJECTIVE Pelvic incidence (PI) is a commonly utilized spinopelvic parameter in the evaluation and treatment of patients with spinal deformity and is believed to be a fixed parameter. However, a fixed PI assumes that there is no motion across the sacroiliac (SI) joint, which has been disputed in recent literature. The objective of this study was to determine if patients with SI joint vacuum sign have a change in PI between the supine and standing positions. METHODS A retrospective chart review identified patients with a standing radiograph, supine radiograph, and CT scan encompassing the SI joints within a 6-month period. Patients were grouped according to their SI joints having either no vacuum sign, unilateral vacuum sign, or bilateral vacuum sign. PI was measured by two independent reviewers. RESULTS Seventy-three patients were identified with an average age of 66 years and a BMI of 30 kg/m2. Patients with bilateral SI joint vacuum sign (n = 27) had an average absolute change in PI of 7.2° (p < 0.0001) between the standing and supine positions compared to patients with unilateral SI joint vacuum sign (n = 20) who had a change of 5.2° (p = 0.0008), and patients without an SI joint vacuum sign (n = 26) who experienced a change of 4.1° (p = 0.74). ANOVA with post hoc Tukey test showed a statistically significant difference in the change in PI between patients with the bilateral SI joint vacuum sign and those without an SI joint vacuum sign (p = 0.023). The intraclass correlation coefficient between the two reviewers was 0.97 for standing PI and 0.96 for supine PI (p < 0.0001). CONCLUSIONS Patients with bilateral SI joint vacuum signs had a change in PI between the standing and supine positions, suggesting there may be increasing motion across the SI joint with significant joint degeneration.

Study Design: Retrospective Study. Objective: To compare methods of assessing pre-operative bone density to predict risk for osteoporosis related complications (ORC), defined as proximal junctional kyphosis, pseudarthrosis, accelerated adjacent segment disease, reoperation, compression fracture, and instrument failure following spine fusions. Methods: Chart review of primary posterior thoracolumbar or lumbar fusion patients during a 7 year period. Inclusion criteria: preoperative dual-energy x-ray absorptiometry (DXA) test within 1 year and lumbar CT scan within 6 months prior to surgery with minimum of 1 year follow-up. Exclusion criteria: <18 years at time of index procedure, infection, trauma, malignancy, skeletal dysplasia, neuromuscular disorders, or anterior-posterior procedures. Results: 140 patients were included. The average age was 67.9 years, 83 (59.3%) were female, and 45 (32%) had an ORC. There were no significant differences in patient characteristics between those with and without an ORC. Multilevel fusions were associated with ORCs (46.7% vs 26.3%, p = 0.02). Patients with ORCs had lower DXA t-scores (-1.62 vs -1.10, p = 0.003) and average Hounsfield units (HU) (112.1 vs 148.1, p ≤ 0.001). Multivariable binary logistic regression analysis showed lower average HU (Adj. OR 0.00 595% CI 0.0001-0.1713, p = 0.001) was an independent predictor of an ORC. The odds of an ORC increased by 1.7-fold for every 25 point decrease in average HU. Conclusions: The gold standard for assessing bone mineral density has been DXA t-scores, but the best predictor of ORC remains unclear. While both lower t-scores and average HU were associated with ORC, only HU was an independent predictor of ORC.

The spinal column is the most common site for bone metastasis. Vertebral metastases with instability have historically been treated with corpectomy of the affected vertebral body and adjacent intervertebral discs, and have more recently been treated with separation surgery. With demographics shifting towards an elderly population, a less-invasive surgical approach is necessary for the repair of vertebral defects. We modified a previously reported expandable hollow cage composed of an oligo[poly(ethylene glycol) fumarate] (OPF) containment system that could be delivered via a posterior-only approach. Then, the polymer of interest, poly (methyl methacrylate) (PMMA) bone cement, was injected into the lumen of the cage after expansion to form an OPF/PMMA cage. We compared six different cage formulations to account for vertebral body and defect size, and performed a cage characterization via expansion kinetics and mechanical testing evaluations. Additionally, we investigated the feasibility of the OPF/PMMA cage in providing spine stability via kinematic analyses. The in-vitro placement of the implant using our OPF/PMMA cage system showed improvement and mechanical stability in a flexion motion. The results demonstrated that the formulation and technique presented in the current study have the potential to improve surgical outcomes in minimally invasive procedures on the spine.

Study Design: Retrospective case series. Objective: Sacral insufficiency fracture is a rare and serious complication following lumbar spine instrumented fusion. The purpose of this study was to describe the patient characteristics, presentation, evaluation, treatment options, and outcomes for patients with sacral insufficiency fracture after short-segment lumbosacral fusion. Methods: Six patients from our institutional database and 16 patients from literature review were identified with a sacral insufficiency fracture after short-segment (L4-S1 or L5-S1) lumbar fusion within 1 year of surgery. Results: Patients were 55% female with a mean age of 58 years and body mass index of 30 kg/m 2 . Osteoporosis or osteopenia was the most common comorbidity (85%). Half of patients sustained a sacral fracture after surgery from a posterior approach, while the others had anterior or anterior-posterior surgery. Mean time to fracture was 42 days with patients clinically presenting with new sacral pain (86%), radiculopathy (60%), or neurologic deficit (5%). Ultimately, 73% of patients underwent operative fixation often involving extension of the construct (75%) and fusion to the pelvis (69%). Men ( P = .02) and patients with new radicular pain or neurologic deficit ( P = .01) were more likely to undergo revision surgical treatment while women over 50 years of age were more likely to be treated conservatively ( P = .003). Conclusions: Spine surgeons should monitor for sacral insufficiency fracture as a source of new-onset pain in the postoperative period in patients with a short segment fusion to the sacrum. The recognition of this complication should prompt an assessment of bone health and management of underlying bone fragility.