Cari M. Whyne

Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases

The use of stereotactic body radiotherapy for metastatic spinal tumours is increasing. Serious adverse events for this treatment include vertebral compression fracture (VCF) and radiation myelopathy. Although VCF is a fairly low-risk adverse event (approximately 5% risk) after conventional radiotherapy, crude risk estimates for VCF after spinal SBRT range from 11% to 39%. In this Review, we summarise the evidence and predictive factors for VCF induced by spinal SBRT, review the pathophysiology of VCF in the metastatic spine, and discuss strategies used to prevent and manage this potentially disabling complication.

Proximal tibial fracture stability with intramedullary nail fixation using oblique interlocking screws

Objectives The purpose of this study was to evaluate the mechanical stability of oblique interlocking screws in supplementing intramedullary nail fixation of high proximal tibial fractures. Design In vitro experimental testing. Setting Orthopaedic biomechanics laboratory, Sunnybrook and Womens College Health Sciences Center. Participants Ten paired fresh-frozen human cadaver tibiae. Intervention One tibia of each pair was randomized to be instrumented with an intramedullary nail (M/DN; Zimmer, Warsaw, Indiana), while the other was stabilized with a 13-hole stainless steel lateral tibial head plate (Synthes AO/ASIF). Specimens were tested in varus-valgus (v/v), flexion-extension (f/e) and torsion, before and after a 2-cm gap osteotomy was performed in the proximal segment. Testing of the nailed tibiae was performed with and without oblique proximal screws. Bone density was physically determined by removing a core of trabecular bone from the distal end of each tibia following testing. Main Outcome Measurement Biomechanical construct stability. Results The addition of the proximally placed oblique screws increased the stability of the nail construct in v/v by 50% (6.8 mm, P < 0.05), in f/e by 47% (7.2 mm, P < 0.05), and in torsion by 18% (3.0°, P < 0.05). There was no significant difference observed between the stability of the intramedullary nail construct with oblique screws and the plated construct. Trabecular bone density had a significant effect in reducing stability (P < 0.05) in nail and plate fixation. Conclusion The addition of oblique interlocking screws significantly improves the stability of a nailed proximal tibia fracture and provides comparable stability to a plate osteosynthesis.

T-Lymphocytes Enable Osteoblast Maturation via IL-17F during the Early Phase of Fracture Repair

While it is well known that the presence of lymphocytes and cytokines are important for fracture healing, the exact role of the various cytokines expressed by cells of the immune system on osteoblast biology remains unclear. To study the role of inflammatory cytokines in fracture repair, we studied tibial bone healing in wild-type and Rag1−/− mice. Histological analysis, µCT stereology, biomechanical testing, calcein staining and quantitative RNA gene expression studies were performed on healing tibial fractures. These data provide support for Rag1−/− mice as a model of impaired fracture healing compared to wild-type. Moreover, the pro-inflammatory cytokine, IL-17F, was found to be a key mediator in the cellular response of the immune system in osteogenesis. In vitro studies showed that IL-17F alone stimulated osteoblast maturation. We propose a model in which the Th17 subset of T-lymphocytes produces IL-17F to stimulate bone healing. This is a pivotal link in advancing our current understanding of the molecular and cellular basis of fracture healing, which in turn may aid in optimizing fracture management and in the treatment of impaired bone healing.

Biomechanical comparison of intramedullary nail and blade plate fixation for tibiotalocalcaneal arthrodesis

Tibiotalocalcaneal arthrodesis is used to manage severe bone loss, arthritis, and/or instability. The goal is to relieve pain through a stable, well-aligned hindfoot and ankle. The purpose of this study was 2-fold: to biomechanically compare 1) initial stability, and 2) the effect of bone density on the stability of intramedullary nail and blade plate fixation in tibiotalocalcaneal arthrodesis. Design: Biomechanical study using anatomic specimens. Methods: Ankle and subtalar joint capsules were exposed for 7 pairs of fresh-frozen anatomic specimens. One ankle from each pair was instrumented with an interlocked intramedullary nail inserted retrograde across the subtalar and ankle joint while the contralateral hind foot was stabilized with a lateral cannulated blade plate. Specimen stability was tested in plantar/dorsiflexion and inversion/eversion to a maximum bending moment of 12 Nm and in internal/external rotation to a maximum torque of 7 Nm. Physical measurements of bone density were made to determine its effect on stability. Main Outcome Measures: Maximum angular displacement of the constructs in plantarflexion, dorsiflexion, inversion, eversion, internal rotation, and external rotation. Results: No significant differences were observed between the plated and nailed constructs in the 3 loading configurations (Power = 0.77). Only 6 pairs were included in the results because of fixation failures. A small but significant reduction in internal rotation alone of 1.8° was found with the plated compared with the nailed construct (P = 0.045). Reduced stability was associated with lower bone density in torsion and inversion/eversion in the plated constructs (r2 = 0.67- 0.87) with a similar trend seen in torsion in the nailed constructs (r2 = 0.5). Conclusion: Initial construct stabilities and the effect of reduced bone density were found to be similar between the blade plate and the intramedullary nail in tibiotalocalcaneal arthrodesis, thus implant choice may be based on other clinical factors, such as surgeon preference or soft- tissue status.

Burst fracture in the metastatically involved spine: Development, validation, and parametric analysis of a three-dimensional poroelastic finite-element model

Study Design. A finite-element study and in vitro experimental validation was performed for a parametric investigation of features that contribute to burst fracture risk in the metastatically involved spine. Objectives. To develop and validate a three-dimensional poroelastic model of a metastatically compromised vertebral segment, to evaluate the effect of lytic lesions on vertebral strains and pressures, and to determine the influence of loading and motion segment status (bone density, pedicle involvement, disc degeneration, and tumor size) on the relative risk of burst fracture initiation. Summary of Background Data. Finite-element analysis has been used successfully to predict failure loads and fracture patterns for bone. Although models for vertebra affected with tumors have been presented, these have not been thoroughly validated experimentally. Consequently, their predictive capabilities remain uncertain. Methods. A three-dimensional poroelastic finite-element model of the first lumbar vertebra and adjacent intervertebral discs, including a tumor of variable size, was developed. To validate the model, 12 cadaver spinal motion segments were tested in axial compression, in intact condition, and with simulated osteolytic defects. Features of the validated model were parametrically varied to investigate the effects of tumor size, trabecular bone density, pedicle involvement, applied loads, loading rates, and disc degeneration using outcome variables of vertebral bulge and vertebral axial deformation. Results. Consistent trends between the experimental data and model predictions were observed. Overall, the model results suggest that tumor size contributes most toward the risk of initiating burst fracture, followed by the applied load magnitude and bone density. Conclusions. The parametric analysis suggests that the principal factors affecting the initiation of burst fracture in metastatically affected vertebrae are tumor size, magnitude of spinal loading, and bone density. Consequently, patient-specific measures of these factors should be factored into decisions regarding clinical prophylaxis. Pedicle involvement or disc degeneration was less important according to the outcome measures in this study.

Hierarchical Model of Fibrillar Collagen Organization for Interpreting the Second-Order Susceptibility Tensors in Biological Tissue

The second-order nonlinear polarization properties of fibrillar collagen in various rat tissues (vertebrae, tibia, tail tendon, dermis, and cornea) are investigated with polarization-dependent second-harmonic generation (P-SHG) microscopy. Three parameters are extracted: the second-order susceptibility ratio, R = [Formula: see text] ; a measure of the fibril distribution asymmetry, |A|; and the weighted-average fibril orientation, . A hierarchical organizational model of fibrillar collagen is developed to interpret the second-harmonic generation polarization properties. Highlights of the model include: collagen type (e.g., type-I, type-II), fibril internal structure (e.g., straight, constant-tilt), and fibril architecture (e.g., parallel fibers, intertwined, lamellae). Quantifiable differences in internal structure and architecture of the fibrils are observed. Occurrence histograms of R and |A| distinguished parallel from nonparallel fibril distributions. Parallel distributions possessed low parameter values and variability, whereas nonparallel distributions displayed an increase in values and variability. From the P-SHG parameters of vertebrae tissue, a three-dimensional reconstruction of lamellae of intervertebral disk is presented.

Quantitative characterization of metastatic disease in the spine. Part I. Semiautomated segmentation using atlas-based deformable registration and the level set method

Quantitative assessment of metastatic disease in bone is often considered immeasurable and, as such, patients with skeletal metastases are often excluded from clinical trials. In order to effectively quantify the impact of metastatic tumor involvement in the spine, accurate segmentation of the vertebra is required. Manual segmentation can be accurate but involves extensive and time-consuming user interaction. Potential solutions to automating segmentation of metastatically involved vertebrae are demons deformable image registration and level set methods. The purpose of this study was to develop a semiautomated method to accurately segment tumor-bearing vertebrae using the aforementioned techniques. By maintaining morphology of an atlas, the demons-level set composite algorithm was able to accurately differentiate between trans-cortical tumors and surrounding soft tissue of identical intensity. The algorithm successfully segmented both the vertebral body and trabecular centrum of tumor-involved and healthy vertebrae. This work validates our approach as equivalent in accuracy to an experienced user.

A Novel Thiol-Modified Hyaluronan and Elastin-Like Polypetide Composite Material for Tissue Engineering of the Nucleus Pulposus of the Intervertebral Disc

Study Design. Biomechanical, in vitro, and initial in vivo evaluation of a thiol-modified hyaluronan (TM-HA) and elastin-like polypeptide (ELP) composite hydrogel for nucleus pulposus (NP) tissue engineering. Objective. To investigate the utility of a TM-HA and ELP composite material as a potential tissue-engineering scaffold to reconstitute the NP in early degenerative disc disease (DDD) on the basis of both biomechanical and biologic parameters. Summary of Background Data. DDD is a common ailment with enormous medical, psychosocial, and economic ramifications. Only end-stage surgical therapies are currently widely available. A less invasive, early stage therapy may provide a clinically relevant treatment option. Methods. TM-HA and ELP were combined in various concentrations and cross-linked using poly (ethylene glycol) diacrylate. Resulting materials were evaluated biomechanically using confined com-pression to determine biphasic material properties. In vitro cell culture with human intervertebral disc (IVD) cells seeded within TM-HA/ELP scaffolds was analyzed for cell viability and phenotype. The hydrogels’ materials were evaluated in an established New Zealand White (NZW) rabbit model of DDD. Results. The addition of ELP to TM-HA–based hydrogels resulted in a stiffer construct, which is less stiff than native NP but has time-dependant loading characteristics that may be desirable when injected into the IVD. In vitro experiments demonstrated 70% cell viability at 3 weeks with apparent maintenance of phenotype on the basis of morphologic and immunohistochemical data. The addition of ELP had a positive desirable biomechanical effect but did not have a significant positive or negative biologic effect on cell activity. The in vivo feasibility study demonstrated favorable material characteristics and biocompatibility for application as a minimally invasive injectable NP supplement. Conclusions. TM-HA–based hydrogels provide a hospitable environment for human IVD cells and have material characteristics, particularly when supplemented with ELPs that are attractive for potential application as an injectable NP supplement.

Intraoperative cone-beam CT for image-guided tibial plateau fracture reduction.

Objectives: A mobile isocentric C-arm was modified in our laboratory in collaboration with Siemens Medical Solutions to include a large-area flat-panel detector providing multi-mode fluoroscopy and cone-beam CT (CBCT) imaging. This technology is an important advance over existing intraoperative imaging (e.g., Iso-C3D), offering superior image quality, increased field of view, higher spatial resolution, and soft-tissue visibility. The aim of this study was to assess the systems performance and image quality in tibial plateau (TP) fracture reconstruction. Methods: Three TP fractures were simulated in fresh-frozen cadaveric knees through combined axial loading and lateral impact. The fractures were reduced through a lateral approach and assessed by fluoroscopy. The reconstruction was then assessed using CBCT. If necessary, further reduction and localization of remaining displaced bone fragments was performed using CBCT images for guidance. CBCT image quality was assessed with respect to projection speed, dose and filtering technique. Results: CBCT imaging provided exquisite visualization of articular details, subtle fragment detection and localization, and confirmation of reduction and implant placement. After fluoroscopic images indicated successful initial reduction, CBCT imaging revealed areas of malalignment and displaced fragments. CBCT facilitated fragment localization and improved anatomic reduction. CBCT image noise increased gradually with reduced dose, but little difference in images resulted from increased projections. High-resolution reconstruction provided better delineation of plateau depressions. Conclusion: This study demonstrated a clear advantage of intraoperative CBCT over 2D fluoroscopy and Iso-C3D in TP fracture fixation. CBCT imaging provided benefits in fracture type diagnosis, localization of fracture fragments, and intraoperative 3D confirmation of anatomic reduction.

Biomechanically derived guideline equations for burst fracture risk prediction in the metastatically involved spine.

Methods to quantify burst fracture risk and neurologic deficit for patients with spinal metastases have not been well defined. This study aims to develop objective biomechanically based guidelines to quantify metastatic burst fracture risk. An experimentally validated finite element model of a human lumbar motion segment was used to simulate burst fracture. Through parametric analysis, the behavior of metastatically involved vertebrae was quantified and a formula to relate patient-specific variables to burst fracture risk defined. The equation-based guidelines were able to describe the mechanical behavior of the metastatically involved vertebral model (R2 = 0.97) reflecting the risk and mechanism of fracture. Vertebral density was found to influence the mechanism of burst fracture with respect to endplate failure. These analyses provide clinically feasible equation-based guidelines for burst fracture risk assessment in the metastatically involved spine.