Female Human Spines with Simulated Osteolytic Defects: CT-based Structural Analysis of Vertebral Body Strength.

Purpose To evaluate a CT structural analysis protocol (SAP) for estimating the strength of human female cadaveric spines with lytic lesions. Materials and Methods Osteolytic foci was created in the middle vertebra of 44 thoracic and lumbar three-level segments from 11 female cadavers (age range, 50-70 years). The segments underwent CT by using standard clinical protocol and their failure strength was assessed at CT SAP. The spines were mechanically tested to failure in pure axial compression or in compression with torsion. The relationships of defect size, bone mineral density, and predicted failure load (at CT SAP) with measured vertebral strength were assessed with linear regression. Analysis of variance and Tukey test were used to evaluate the effect of region and mechanical test on spine strength. Results With axial compression, CT SAP predictions of vertebral strength correlated with the thoracic (r = 0.84; P < .001) and lumbar (r = 0.85; P < .001) segment-measured strength. Bone mineral density correlated with the lumbar (r = 0.64; P = .003) and thoracic (r, 0.51; P = .050) strength. At compression with torsion, CT SAP predictions of strength were moderately correlated with vertebral strength (r = 0.66; P = .018). At compression with torsion, bone mineral density was not correlated with spinal strength (thoracic and lumbar: r = 0.31 and r = 0.26, respectively; P = .539 and .610, respectively). The lytic focus size (range, 28%-41%) was not associated with vertebral strength. Conclusion CT SAP assessment of strength in vertebrae with lytic lesions correlated with the measured strength of female vertebral bodies. © RSNA, 2018 Online supplemental material is available for this article.

MR diffusion is sensitive to mechanical loading in human intervertebral disks ex vivo.

PURPOSE: To use T2 and diffusion MR to determine the change in the mechanical function of human disks with increased degenerative state. MATERIALS AND METHODS: Spatial changes in T2 and diffusion were quantified in five cadaveric human lumbar disks under compressive loads. Regression models were used to investigate the relationship between the change in MR parameters and the disk's dynamic and viscoelastic properties. RESULTS: Compressive loading caused a significant reduction in the disk's mean diffusivity ([11.3 versus 9.7].10(-4) .mm(2) /s, P < 0.001) but little change in T2 (P < 0.05). Diffusivity and T2 were correlated with the disk's dynamic (P < 0.01 and P < 0.05) and long-term viscoelastic (P < 0.05 and P < 0.05) stiffness. Diffusivity but not T2, was correlated with its viscoelastic dampening (r(2) = 0.45, P < 0.01) and instantaneous stiffness (r(2) = 0.44, P < 0.05). Nucleus diffusivity was significantly higher than the annulus's (-21% to -4%, P < 0.01). MR-estimated hydration was correlated with the instantaneous viscoelastic stiffness of the nucleus (r(2) = 0.35, P < 0.05) and the dynamic (r(2) = 0.44, P < 0.05) and long-term viscoelastic (r(2) = 0.42, P < 0.05) stiffness in the annulus. T2 correlated with diffusivity at low load (r(2) = 0.66, P < 0.05), but not at high load. CONCLUSION: The strong correlations between diffusivity and the rheological assessments of disk mechanics suggest that MR might permit quantitative assessment of disk functional status and structural integrity.

CT-based finite element simulating spatial bone damage accumulation predicts metastatic human vertebrae strength and stiffness.

Introduction: Pathologic vertebral fractures are devastating for patients with spinal metastases. However, the mechanical process underlying these fractures is poorly understood, limiting physician's ability to predict which vertebral bodies will fail. Method: Here, we show the development of a damage-based finite element framework producing highly reliable pathologic vertebral strength and stiffness predictions from X-Ray computed tomography (CT) data. We evaluated the performance of specimen-specific material calibration vs. global material calibration across osteosclerotic, osteolytic, and mixed lesion vertebrae that we derived using a machine learning approach. Results: The FE framework using global calibration strongly predicted the pathologic vertebrae stiffness (R 2 = 0.90, p < 0.0001) and strength (R 2 = 0.83, p = 0.0002) despite the remarkable variance in the pathologic bone structure and density. Specimen-specific calibration produced a near-perfect prediction of both stiffness and strength (R 2 = 0.99, p < 0.0001, for both), validating the FE approach. The FE damage-based simulations highlighted the differences in the pattern of spatial damage evolution between osteosclerotic and osteolytic vertebral bodies. Discussion: With failure, the FE simulation suggested a common damage evolution pathway progressing largely localized to the low bone modulus regions within the vertebral volume. Applying this FE approach may allow us to predict the onset and anatomical location of vertebral failure, which is critical for developing image-based diagnostics of impending pathologic vertebral fractures.

The effects of design and positioning of carbon fiber lumbar interbody cages and their subsidence in vertebral bodies.

STUDY DESIGN: A biomechanical study using human cadaveric lumbar spines. OBJECTIVES: To determine the strength and stiffness of 3 carbon fiber cage designs in axial compression. To assess the effects of bone mineral density (BMD) on vertebral endplate failure with respect to the different cage patterns. SUMMARY OF BACKGROUND DATA: Unilateral transforaminal approaches are gaining popularity compared with posterolateral lumbar interbody fusion. With differences in the inherent strengths of each quadrant of the endplate, the effect of different cage designs and their location on the endplate may affect subsidence and fusion success. METHODS: BMD measurements were obtained from 30 human spinal segments from L3 to L5. Discectomies were performed and cages were placed on the cephalad endplate of each vertebra in 3 configurations: 2 small posterolateral rectangular cages; 1 small anterior banana cage; and 1 small central rectangular cage. Each segment was tested under compression until endplate failure was recorded. Two-way analysis of variance was used to test for the effects of cage design on cage subsidence and endplate failure. Analysis of covariance was conducted to test for the effects of age, BMD, and vertebral levels on the failure load and stiffness for each cage design. RESULTS: Cage design was not significant in affecting failure force across the endplate. There were insignificant differences comparing stiffness in compression for the 3 different cage placements patterns. Low BMD adversely affected failure force and construct stiffness across all 3 cage patterns. CONCLUSIONS: Cage design and position do not significantly affect failure of the construct or stiffness in compression across the endplate. BMD significantly affects both failure forces and stiffness but is not dependent on the positioning or design of the cage.

Influence of Metastatic Bone Lesion Type and Tumor Origin on Human Vertebral Bone Architecture, Matrix Quality, and Mechanical Properties.

Metastatic spine disease is incurable, causing increased vertebral fracture risk and severe patient morbidity. Here, we demonstrate that osteolytic, osteosclerotic, and mixed bone metastasis uniquely modify human vertebral bone architecture and quality, affecting vertebral strength and stiffness. Multivariable analysis showed bone metastasis type dominates vertebral strength and stiffness changes, with neither age nor gender having an independent effect. In osteolytic vertebrae, bone architecture rarefaction, lower tissue mineral content and connectivity, and accumulation of advanced glycation end-products (AGEs) affected low vertebral strength and stiffness. In osteosclerotic vertebrae, high trabecular number and thickness but low AGEs, suggesting a high degree of bone remodeling, yielded high vertebral strength. Our study found that bone metastasis from prostate and breast primary cancers differentially impacted the osteosclerotic bone microenvironment, yielding altered bone architecture and accumulation of AGEs. These findings indicate that therapeutic approaches should target the restoration of bone structural integrity. © 2022 American Society for Bone and Mineral Research (ASBMR).

Improved estimates of strength and stiffness in pathologic vertebrae with bone metastases using CT-derived bone density compared with radiographic bone lesion quality classification.

OBJECTIVE: The aim of this study was to compare the ability of 1) CT-derived bone lesion quality (classification of vertebral bone metastases [BM]) and 2) computed CT-measured volumetric bone mineral density (vBMD) for evaluating the strength and stiffness of cadaver vertebrae from donors with metastatic spinal disease. METHODS: Forty-five thoracic and lumbar vertebrae were obtained from cadaver spines of 11 donors with breast, esophageal, kidney, lung, or prostate cancer. Each vertebra was imaged using microCT (21.4 µm), vBMD, and bone volume to total volume were computed, and compressive strength and stiffness experimentally measured. The microCT images were reconstructed at 1-mm voxel size to simulate axial and sagittal clinical CT images. Five expert clinicians blindly classified the images according to bone lesion quality (osteolytic, osteoblastic, mixed, or healthy). Fleiss' kappa test was used to test agreement among 5 clinical raters for classifying bone lesion quality. Kruskal-Wallis ANOVA was used to test the difference in vertebral strength and stiffness based on bone lesion quality. Multivariable regression analysis was used to test the independent contribution of bone lesion quality, computed vBMD, age, gender, and race for predicting vertebral strength and stiffness. RESULTS: A low interrater agreement was found for bone lesion quality (κ = 0.19). Although the osteoblastic vertebrae showed significantly higher strength than osteolytic vertebrae (p = 0.0148), the multivariable analysis showed that bone lesion quality explained 19% of the variability in vertebral strength and 13% in vertebral stiffness. The computed vBMD explained 75% of vertebral strength (p < 0.0001) and 48% of stiffness (p < 0.0001) variability. The type of BM affected vBMD-based estimates of vertebral strength, explaining 75% of strength variability in osteoblastic vertebrae (R2 = 0.75, p < 0.0001) but only 41% in vertebrae with mixed bone metastasis (R2 = 0.41, p = 0.0168), and 39% in osteolytic vertebrae (R2 = 0.39, p = 0.0381). For vertebral stiffness, vBMD was only associated with that of osteoblastic vertebrae (R2 = 0.44, p = 0.0024). Age and race inconsistently affected the model's strength and stiffness predictions. CONCLUSIONS: Pathologic vertebral fracture occurs when the metastatic lesion degrades vertebral strength, rendering it unable to carry daily loads. This study demonstrated the limitation of qualitative clinical classification of bone lesion quality for predicting pathologic vertebral strength and stiffness. Computed CT-derived vBMD more reliably estimated vertebral strength and stiffness. Replacing the qualitative clinical classification with computed vBMD estimates may improve the prediction of vertebral fracture risk.

Evaluation of Load-To-Strength Ratios in Metastatic Vertebrae and Comparison With Age- and Sex-Matched Healthy Individuals.

Vertebrae containing osteolytic and osteosclerotic bone metastases undergo pathologic vertebral fracture (PVF) when the lesioned vertebrae fail to carry daily loads. We hypothesize that task-specific spinal loading patterns amplify the risk of PVF, with a higher degree of risk in osteolytic than in osteosclerotic vertebrae. To test this hypothesis, we obtained clinical CT images of 11 cadaveric spines with bone metastases, estimated the individual vertebral strength from the CT data, and created spine-specific musculoskeletal models from the CT data. We established a musculoskeletal model for each spine to compute vertebral loading for natural standing, natural standing + weights, forward flexion + weights, and lateral bending + weights and derived the individual vertebral load-to-strength ratio (LSR). For each activity, we compared the metastatic spines' predicted LSRs with the normative LSRs generated from a population-based sample of 250 men and women of comparable ages. Bone metastases classification significantly affected the CT-estimated vertebral strength (Kruskal-Wallis, p < 0.0001). Post-test analysis showed that the estimated vertebral strength of osteosclerotic and mixed metastases vertebrae was significantly higher than that of osteolytic vertebrae (p = 0.0016 and p = 0.0003) or vertebrae without radiographic evidence of bone metastasis (p = 0.0010 and p = 0.0003). Compared with the median (50%) LSRs of the normative dataset, osteolytic vertebrae had higher median (50%) LSRs under natural standing (p = 0.0375), natural standing + weights (p = 0.0118), and lateral bending + weights (p = 0.0111). Surprisingly, vertebrae showing minimal radiographic evidence of bone metastasis presented significantly higher median (50%) LSRs under natural standing (p < 0.0001) and lateral bending + weights (p = 0.0009) than the normative dataset. Osteosclerotic vertebrae had lower median (50%) LSRs under natural standing (p < 0.0001), natural standing + weights (p = 0.0005), forward flexion + weights (p < 0.0001), and lateral bending + weights (p = 0.0002), a trend shared by vertebrae with mixed lesions. This study is the first to apply musculoskeletal modeling to estimate individual vertebral loading in pathologic spines and highlights the role of task-specific loading in augmenting PVF risk associated with specific bone metastatic types. Our finding of high LSRs in vertebrae without radiologically observed bone metastasis highlights that patients with metastatic spine disease could be at an increased risk of vertebral fractures even at levels where lesions have not been identified radiologically.

Large Lytic Defects Produce Kinematic Instability and Loss of Compressive Strength in Human Spines: An in Vitro Study.

BACKGROUND: In patients with spinal metastases, kinematic instability is postulated to be a predictor of pathologic vertebral fractures. However, the relationship between this kinematic instability and the loss of spinal strength remains unknown. METHODS: Twenty-four 3-level thoracic and lumbar segments from 8 cadaver spines from female donors aged 47 to 69 years were kinematically assessed in axial compression (180 N) and axial compression with a flexion or extension moment (7.5 Nm). Two patterns of lytic defects were mechanically simulated: (1) a vertebral body defect, corresponding to Taneichi model C (n = 13); and (2) the model-C defect plus destruction of the ipsilateral pedicle and facet joint, corresponding to Taneichi model E (n = 11). The kinematic response was retested, and compression strength was measured. Two-way repeated-measures analysis of variance was used to test the effect of each model on the kinematic response of the segment. Multivariable linear regression was used to test the association between the kinematic parameters and compressive strength of the segment. RESULTS: Under a flexion moment, and for both models C and E, the lesioned spines exhibited greater flexion range of motion (ROM) and axial translation than the control spines. Both models C and E caused lower extension ROM and greater axial, sagittal, and transverse translation under an extension moment compared with the control spines. Two-way repeated-measures analysis revealed that model E, compared with model C, caused significantly greater changes in extension and torsional ROM under an extension moment, and greater sagittal translation under a flexion moment. For both models C and E, greater differences in flexion ROM and sagittal translation under a flexion moment, and greater differences in extension ROM and in axial and transverse translation under an extension moment, were associated with lower compressive strength of the lesioned spines. CONCLUSIONS: Critical spinal lytic defects result in kinematic abnormalities and lower the compressive strength of the spine. CLINICAL RELEVANCE: This experimental study demonstrates that lytic foci degrade the kinematic stability and compressive strength of the spine. Understanding the mechanisms for this degradation will help to guide treatment decisions that address inferred instability and fracture risk in patients with metastatic spinal disease.

Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection.

HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20-30% loss of weight at day 7 and full recovery at days 11-13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses.

The effects of metastatic lesion on the structural determinants of bone: Current clinical and experimental approaches.

Metastatic bone disease is incurable with an associated increase in skeletal-related events, particularly a 17-50% risk of pathologic fractures. Current surgical and oncological treatments are palliative, do not reduce overall mortality, and therefore optimal management of adults at risk of pathologic fractures presents an unmet medical need. Plain radiography lacks specificity and may result in unnecessary prophylactic fixation. Radionuclide imaging techniques primarily supply information on the metabolic activity of the tumor or the bone itself. Magnetic resonance imaging and computed tomography provide excellent anatomical and structural information but do not quantitatively assess bone matrix. Research has now shifted to developing unbiased data-driven tools that can predict risk of impending fractures and guide individualized treatment decisions. This review discusses the state-of-the-art in clinical and experimental approaches for prediction of pathologic fractures with bone metastases. Alterations in bone matrix quality are associated with an age-related increase in skeletal fragility but the impact of metastases on the intrinsic material properties of bone is unclear. Engineering-based analyses are non-invasive with the capability to evaluate oncological treatments and predict failure due to the progression of metastasis. The combination of these approaches may improve our understanding of the underlying deterioration in mechanical performance.

Finite element models can reproduce the effect of nucleotomy on the multi-axial compliance of human intervertebral discs.

Finite element (FE) models can unravel the link between intervertebral disc (IVD) degeneration and its mechanical behaviour. Nucleotomy may provide the data required for model verification. Three human IVDs were scanned with MRI and tested in multiple loading scenarios, prior and post nucleotomy. The resulting data was used to generate, calibrate, and verify the FE models. Nucleotomy increased the experimental range of motion by 26%, a result reproduced by the FE simulation within a 5% error. This work demonstrates the ability of FE models to reproduce the mechanical compliance of human IVDs prior and post nucleotomy.

Conventional finite element models estimate the strength of metastatic human vertebrae despite alterations of the bone's tissue and structure.

INTRODUCTION: Pathologic vertebral fractures are a major clinical concern in the management of cancer patients with metastatic spine disease. These fractures are a direct consequence of the effect of bone metastases on the anatomy and structure of the vertebral bone. The goals of this study were twofold. First, we evaluated the effect of lytic, blastic and mixed (both lytic and blastic) metastases on the bone structure, on its material properties, and on the overall vertebral strength. Second, we tested the ability of bone mineral content (BMC) measurements and standard FE methodologies to predict the strength of real metastatic vertebral bodies. METHODS: Fifty-seven vertebral bodies from eleven cadaver spines containing lytic, blastic, and mixed metastatic lesions from donors with breast, esophageal, kidney, lung, or prostate cancer were scanned using micro-computed tomography (µCT). Based on radiographic review, twelve vertebrae were selected for nanoindentation testing, while the remaining forty-five vertebrae were used for assessing their compressive strength. The µCT reconstruction was exploited to measure the vertebral BMC and to establish two finite element models. 1) a micro finite element (µFE) model derived at an image resolution of 24.5 µm and 2) homogenized FE (hFE) model derived at a resolution of 0.98 mm. Statistical analyses were conducted to measure the effect of the bone metastases on BV/TV, indentation modulus (Eit), ratio of plastic/total work (WPl/Wtot), and in vitro vertebral strength (Fexp). The predictive value of BMC, µFE stiffness, and hFE strength were evaluated against the in vitro measurements. RESULTS: Blastic vertebral bodies exhibit significantly higher BV/TV compared to the mixed (p = 0.0205) and lytic (p = 0.0216) vertebral bodies. No significant differences were found between lytic and mixed vertebrae (p = 0.7584). Blastic bone tissue exhibited a 5.8% lower median Eit (p< 0.001) and a 3.3% lower median Wpl/Wtot (p<0.001) compared to non-involved bone tissue. No significant differences were measured between lytic and non-involved bone tissues. Fexp ranged from 1.9 to 13.8 kN, was strongly associated with hFE strength (R2=0.78, p< 0.001) and moderately associated with BMC (R2=0.66, p< 0.001) and µFE stiffness (R2=0.66, p< 0.001), independently of the lesion type. DISCUSSION: Our findings show that tumour-induced osteoblastic metastases lead to slightly, but significantly lower bone tissue properties compared to controls, while osteolytic lesions appear to have a negligible impact. These effects may be attributed to the lower mineralization and woven nature of bone forming in blastic lesions whilst the material properties of bone in osteolytic vertebrae appeared little changed. The moderate association between BMC- and FE-based predictions to fracture strength suggest that vertebral strength is affected by the changes of bone mass induced by the metastatic lesions, rather than altered tissue properties. In a broader context, standard hFE approaches generated from CTs at clinical resolution are robust to the lesion type when predicting vertebral strength. These findings open the door for the development of FE-based prediction tools that overcomes the limitations of BMC in accounting for shape and size of the metastatic lesions. Such tools may help clinicians to decide whether a patient needs the prophylactic fixation of an impending fracture.

Preventing distal pullout of posterior spine instrumentation in thoracic hyperkyphosis: a biomechanical analysis.

STUDY DESIGN: An in vitro biomechanical study. OBJECTIVE: Compare the mechanical behavior of 5 different constructs used to terminate dual-rod posterior spinal instrumentation in resisting forward flexion moment. SUMMARY OF BACKGROUND DATA: Failure of the distal fixation construct can be a significant problem for patients undergoing surgical treatment for thoracic hyperkyphosis. We hypothesize that augmenting distal pedicle screws with infralaminar hooks or sublaminar cables significantly increases the strength and stiffness of these constructs. METHODS: Thirty-seven thoracolumbar (T12 to L2) calf spines were implanted with 5 configurations of distal constructs: (1) infralaminar hooks, (2) sublaminar cables, (3) pedicle screws, (4) pedicle screws+infralaminar hooks, and (5) pedicle screws+sublaminar cables. Progressive bending moment was applied to each construct until failure. The mode of failure was noted and the construct's stiffness and failure load determined from the load-displacement curves. RESULTS: Bone density and vertebral dimensions were equivalent among the groups (F=0.1 to 0.9, P>0.05). One-way analysis of covariance (adjusted for differences in density and vertebral dimension) demonstrated that all of the screw-constructs (screw, screw+hook, and screw+cable) exhibited significantly higher stiffness and ultimate failure loads compared with either sublaminar hook or cable alone (P<0.05). The screw+hook constructs (109+/-11 Nm/mm) were significantly stiffer than either screws alone (88+/-17 Nm/mm) or screw+cable (98+/-13 Nm/mm) constructs, P<0.05. Screw+cable construct exhibited significantly higher failure load (1336+/-328 N) compared with screw constructs (1102+/-256 N, P<0.05), whereas not statistically different from the screw+hook construct (1220+/-75 N). The cable and hook constructs failed by laminar fracture, screw construct failed in uniaxial shear (pullout), whereas the screws+(hooks or wires) failed by fracture of caudal vertebral body. CONCLUSIONS: Posterior dual rod constructs fixed distally using pedicle screws were stiffer and stronger in resisting forward flexion compared with cables or hooks alone. Augmenting these screws with either infralaminar hooks or sublaminar cables provided additional resistance to failure.

Diffusion based MR measurements correlates with age-related changes in human intervertebral disks.

BACKGROUND: Understanding the association between MR parameters and age related deterioration in human intervertebral disks forms an important step in the development of clinical diagnostic protocols for disk disease. METHODS: Ten unfixed thoracic and lumbar cadaver disk joints, age 37-81 years were imaged at 9.4 T using T2 relaxation (CPMG) and ADC (DWI spin echo) MR protocols. For each MR parameter, spatial maps were computed from the axial images, with the AF and NP segmented based on the T2 maps. Linear regression tested for the correlation between mean and variance (COV) of T2 and ADC with age in the disk, nucleus and annulus, and the effect of thoracic vs. lumbar spine on these correlations. FINDINGS: In the disk, age negatively correlated with mean ADC (P < 0.001) and positively with COV of ADC (P < 0.001) and T2 (P < 0.05). Age was negatively correlated with mean T2 (P < 0.01), mean ADC (P < 0.001) and positively with COV of ADC (P < 0.001) and T2 (P < 0.05) in the NP and positively correlated with mean T2 (P < 0.05), COV of ADC (P < 0.01) and T2 (P < 0.05) and negatively with mean ADC (P < 0.05) in the AF. Compared to thoracic disks, lumbar disks showed higher mean ADC (P < 0.05), lower mean T2 (P < 0.001) and higher COV of ADC (P < 0.01) and T2 (P < 0.05). INTERPRETATION: Compared to T2, MR diffusion was a more sensitive measure of age mediated changes in disk tissues. Strong differences in the association of MR parameters with age between the lumbar and thoracic suggest that mechanical environment effects tissue specific MR parameters' association with age.

The effect of interbody fusion cage design on the stability of the instrumented spine in response to cyclic loading: an experimental study.

BACKGROUND CONTEXT: In the lumbar spine, end plate preparation for the interbody fusion cages may critically affect the cage's long-term performance. This study investigated the effect of the interbody cage design on the compliance and cage subsidence of instrumented spines under cyclic compression. PURPOSE: We aimed to quantify the role of cage geometry and bone density on the stability of the spinal construct in response to cyclic compressive loads. STUDY DESIGN: Changes in the cage-bone interface and the effect of bone density on these changes were evaluated in a human cadaveric model for three intervertebral cage designs. METHODS: The intervertebral space of 27 functional cadaveric spinal units was instrumented with bilateral linear cages, single anterior conformal cages, or single unilateral oblique cages. Once augmented with a pedicle screw fixation system, the instrumented spine unit was tested under cyclic compression loads (400-1,200 N) to 20,000 cycles at a rate of 2 Hz. Compliance of the cage-bone interface and cage subsidence was computed. Two-way repeated multivariate analysis of variance was used to test the effects of cage design and bone density on the compliance and subsidence of the cages. RESULTS: The anterior conformal shaped cage showed reduced interface stiffness (p<.01) and higher hysteresis (p<.01) and subsidence rate (10%-30%) than the bilateral linear and unilateral oblique-shaped cages. Bone density was not associated with the initial compliance of the cage-bone interface or the rate of cage subsidence. Higher bone density did decrease the rate of reduction in cage-bone interface stiffness under higher cyclic loads for the anterior conformal shaped and unilateral oblique cages. CONCLUSIONS: Cage design and position significantly affected the degradation of the cage-bone interface under cyclic loading. Comparisons of subsidence rate between the different cage designs suggest the peripheral location of the cages, using the stronger peripheral subchondral bone of the apophyseal ring, to be advantageous in preventing the subsidence and failure of the cage-bone interface.

Integrating MRI-based geometry, composition and fiber architecture in a finite element model of the human intervertebral disc.

Intervertebral disc degeneration is a common disease that is often related to impaired mechanical function, herniations and chronic back pain. The degenerative process induces alterations of the disc's shape, composition and structure that can be visualized in vivo using magnetic resonance imaging (MRI). Numerical tools such as finite element analysis (FEA) have the potential to relate MRI-based information to the altered mechanical behavior of the disc. However, in terms of geometry, composition and fiber architecture, current FE models rely on observations made on healthy discs and might therefore not be well suited to study the degeneration process. To address the issue, we propose a new, more realistic FE methodology based on diffusion tensor imaging (DTI). For this study, a human disc joint was imaged in a high-field MR scanner with proton-density weighted (PD) and DTI sequences. The PD image was segmented and an anatomy-specific mesh was generated. Assuming accordance between local principal diffusion direction and local mean collagen fiber alignment, corresponding fiber angles were assigned to each element. Those element-wise fiber directions and PD intensities allowed the homogenized model to smoothly account for composition and fibrous structure of the disc. The disc's in vitro mechanical behavior was quantified under tension, compression, flexion, extension, lateral bending and rotation. The six resulting load-displacement curves could be replicated by the FE model, which supports our approach as a first proof of concept towards patient-specific disc modeling.

Mechanical assessment of the effects of metastatic lytic defect on the structural response of human thoracolumbar spine.

To investigate the effects of a clinical lytic defect on the structural response of human thoracolumbar functional spinal unit. A novel CT-compatible mechanical test system was used to image the deformation of a T12-L1 motion segment and measure the change in strain response under compressive loads ranging from 50 to 750 N. A lytic lesion (LM) with cortex involvement (33% by volume) was introduced to the upper vertebral body and the CT experiments were repeated. Finite element models, established from the CT volumes, were used to investigate the defect's effects on the structural response and the state of principal and shear stresses within the affected and adjacent vertebrae. The lytic lesion resulted in severe loss of the vertebral structural competence, resulting in significant, non-linear, and asymmetric increase in the experimentally measured strains and computed stresses within both vertebrae (p < 0.01). At the cortex, the tensile strains were significantly increased, while compressive strains significantly decreased, (p < 0.05). Both the vertebral bone and cortex regions adjacent to the defect showed significant increase in computed compressive, tensile, and shear stresses (p < 0.01). Changes in stress and strain distribution within the affected and adjacent vertebral bone and the experimentally observed bulging and buckling of the vertebral cortices suggested that initiation of catastrophic vertebral failure may occur under load magnitudes encountered in daily living. Although the effect of LM on the global deformation of the spine was well-predicted, our results show that FE predictions of local strain changes must be carefully assessed for clinical relevance. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1808-1819, 2016.

Effect of the metastatic defect on the structural response and failure process of human vertebrae: an experimental study.

BACKGROUND: Pathologic vertebral fractures are associated with intractable pain, loss of function and high morbidity in patients with metastatic spine disease. However, the failure mechanisms of vertebrae with lytic defects and the failed vertebrae's ability to retain load carrying capacity remain unclear. METHODS: Eighteen human thoracic and lumbar vertebrae with simulated uncontained bone defects were tested under compression-bending loads to failure. Failure was defined as 50% reduction in vertebral body height. The vertebrae were allowed to recover under load and re-tested to failure using the initial criteria. Repeated measure ANOVA was used to test for changes in strength and stiffness parameters. FINDINGS: Vertebral failure occurred via buckling and fracture of the cortex around the defect, followed by collapse of the defect region. Compared to the intact vertebrae, the failed vertebrae exhibited a significant loss in compressive strength (59%, p<0.001), stiffness (53%, p<0.05) and flexion (70%, p<0.01) strength. Significant reduction in anterior-posterior shear (strength (63%, p<0.01) and stiffness (67%, p<0.01)) and lateral bending strength (134%, p<0.05) were similarly recorded. In the intact vertebrae, apart from flexion strength (r(2)=0.63), both compressive and anterior-posterior shear strengths were weakly correlated with their stiffness parameters (r(2)=0.24 and r(2)=0.31). By contrast, in the failed vertebrae, these parameters were strongly correlated, (r(2)=0.91, r(2)=0.86, and r(2)=0.92, p<0.001 respectively). INTERPRETATION: Failure of the vertebral cortex at the defect site dominated the initiation and progression of vertebral failure with the vertebrae failing via a consolidation process of the vertebral bone. Once failed, the vertebrae showed remarkable loss of load carrying capacity.

The degenerative state of the intervertebral disk independently predicts the failure of human lumbar spine to high rate loading: an experimental study.

BACKGROUND: In the elderly, 30%-50% of patients report a fall event to precede the onset of vertebral fractures. The dynamic characteristics of the spine determine the peak forces on the vertebrae in a fall. However, we know little about the effect of intervertebral disk degeneration on the failure of human spines under the high loading rates associated with such falls. We hypothesized that MR estimates of disk hydration and viscoelastic properties will provide better estimates of failure strength than bone density alone. METHODS: Seventeen L1-L3 human spine segments were imaged (magnetic resonance imaging, dual-energy X-ray absorptiometry), their dynamic responses quantified using pendulum based impact, and the spines tested to failure under high rate loading simulating a fall event. The spines' stiffness and damping constants were computed (Kelvin-Voigt model) with disk hydration and geometry assessed from T2 and proton density images. FINDINGS: Under impact, the spines exhibited a second-order underdamped response with stiffness and damping ranging (17.9-754.5) kN/m and (133.6-905.3) Ns/m respectively. Damping, but not stiffness, was negatively correlated with higher ultimate strength (P<0.05). Higher bone mineral density and MR-estimated disk hydration correlated with higher ultimate strength (P<0.01 for both). No such correlations were observed for the T2 values. Adding disk hydration yielded a 20% increase in the model's association with failure load compared to bone density alone (MANOVA, P<0.001). INTERPRETATION: The strong correlation between disk viscoelastic properties and MR-estimated hydration with the spine segments' ultimate strength clearly demonstrates the need to include disk degeneration as part of fracture risk assessment in the elderly spine.

Augmentation of failed human vertebrae with critical un-contained lytic defect restores their structural competence under functional loading: An experimental study.

BACKGROUND: Lytic spinal lesions reduce vertebral strength and may result in their fracture. Vertebral augmentation is employed clinically to provide mechanical stability and pain relief for vertebrae with lytic lesions. However, little is known about its efficacy in strengthening fractured vertebrae containing lytic metastasis. METHODS: Eighteen unembalmed human lumbar vertebrae, having simulated uncontained lytic defects and tested to failure in a prior study, were augmented using a transpedicular approach and re-tested to failure using a wedge fracture model. Axial and moment based strength and stiffness parameters were used to quantify the effect of augmentation on the structural response of the failed vertebrae. Effects of cement volume, bone mineral density and vertebral geometry on the change in structural response were investigated. FINDINGS: Augmentation increased the failed lytic vertebral strength [compression: 85% (P<0.001), flexion: 80% (P<0.001), anterior-posterior shear: 95%, P<0.001)] and stiffness [(40% (P<0.05), 53% (P<0.05), 45% (P<0.05)]. Cement volume correlated with the compressive strength (r(2)=0.47, P<0.05) and anterior-posterior shear strength (r(2)=0.52, P<0.05) and stiffness (r(2)=0.45, P<0.05). Neither the geometry of the failed vertebrae nor its pre-fracture bone mineral density correlated with the volume of cement. INTERPRETATION: Vertebral augmentation is effective in bolstering the failed lytic vertebrae compressive and axial structural competence, showing strength estimates up to 50-90% of historical values of osteoporotic vertebrae without lytic defects. This modest increase suggests that lytic vertebrae undergo a high degree of structural damage at failure, with strength only partially restored by vertebral augmentation. The positive effect of cement volume is self-limiting due to extravasation.