Neurosurgical Treatments for Cancer Pain.

Cancer-related pain is a uniquely challenging entity for treating practitioners for a variety of reasons, including its often severe and medically refractory nature, the emotional and social circumstances surrounding the disease process, and the frequently associated limited life expectancy.

Recalibrating the Glasgow Coma Score as an Age-Adjusted Risk Metric for Neurosurgical Intervention.

BACKGROUND: The Glasgow Coma Scale (GCS) score is the most frequently used neurologic assessment in traumatic brain injury (TBI). The risk for neurosurgical intervention based on GCS is heavily modified by age. The objective is to create a recalibrated Glasgow Coma Scale (GCS) score that accounts for an interaction by age and determine the predictive performance of the recalibrated GCS (rGCS) compared to the standard GCS for predicting neurosurgical intervention. METHODS: This retrospective cohort study utilized the National Trauma Data Bank and included all patients admitted from 2010-2015 with TBI (ICD9 diagnosis code 850-854.19). The study population was divided into 2 subsets: a model development dataset (75% of patients) and a model validation dataset (remaining 25%). In the development dataset, logistic regression models were used to calculate conditional probabilities of having a neurosurgical intervention for each combination of age and GCS score, to develop a point-based risk score termed the rGCS. Model performance was examined in the validation dataset using area under the receiver operating characteristic (AUROC) curves and calibration plots. RESULTS: There were 472,824 patients with TBI. The rGCS ranged from 1-15, where rGCS 15 denotes the baseline risk for neurosurgical intervention (4.4%) and rGCS 1 represents the greatest risk (62.6%). In the validation dataset there was a statistically significant improvement in predictive performance for neurosurgical intervention for the rGCS compared to the standard GCS (AUROC: 0.71 versus 0.67, difference, -0.04, P<0.001), overall and by trauma level designation. The rGCS was better calibrated than the standard GCS score. CONCLUSIONS: The relationship between GCS score and neurosurgical intervention is significantly modified by age. A revision to the GCS that incorporates age, the rGCS, provides risk of neurosurgical intervention that has better predictive performance than the standard ED GCS score.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Neuroablative Procedures for Patients With Cancer Pain.

BACKGROUND: Managing cancer pain once it is refractory to conventional treatment continues to challenge caregivers committed to serving those who are suffering from a malignancy. Although neuromodulation has a role in the treatment of cancer pain for some patients, these therapies may not be suitable for all patients. Therefore, neuroablative procedures, which were once a mainstay in treating intractable cancer pain, are again on the rise. This guideline serves as a systematic review of the literature of the outcomes following neuroablative procedures. OBJECTIVE: To establish clinical practice guidelines for the use of neuroablative procedures to treat patients with cancer pain. METHODS: A systematic review of neuroablative procedures used to treat patients with cancer pain from 1980 to April 2019 was performed using the United States National Library of Medicine PubMed database, EMBASE, and Cochrane CENTRAL. After inclusion criteria were established, full text articles that met the inclusion criteria were reviewed by 2 members of the task force and the quality of the evidence was graded. RESULTS: In total, 14 646 relevant abstracts were identified by the literature search, from which 189 met initial screening criteria. After full text review, 58 of the 189 articles were included and subdivided into 4 different clinical scenarios. These include unilateral somatic nociceptive/neuropathic body cancer pain, craniofacial cancer pain, midline subdiaphragmatic visceral cancer pain, and disseminated cancer pain. Class II and III evidence was available for these 4 clinical scenarios. Level III recommendations were developed for the use of neuroablative procedures to treat patients with cancer pain. CONCLUSION: Neuroablative procedures may be an option for treating patients with refractory cancer pain. Serious adverse events were reported in some studies, but were relatively uncommon. Improved imaging, refinements in technique and the availability of new lesioning modalities may minimize the risks of neuroablation even further.The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-on-neuroablative-procedures-patients-wi.

Neurosurgical Management of Cancer Facial Pain.

Facial pain occurs in approximately 80% of patients with head and neck cancers. Pain in these settings may result directly from the tumor, or indirectly as a side effect of oncological treatment of the tumor. Optimizing treatment for cancer pain of the face, therefore, involves a variety of diagnostic and treatment considerations, with the development of a successful treatment algorithm dependent on accurate diagnosis of the anatomical location of the pain, its relationship to the facial pain pathway, the type of pain being treated and, finally, patient's prognosis and preference for treatment modality. Beyond direct treatments to reduce tumor burden, a wide variety of neuro-ablative and neuro-augmentative approaches are available that may be tailored to a patient's specific pain syndrome and individual clinical context, taking into account the patient's treatment goals, life expectancy, other cancer-related medical problems, and end-of-life issues.

A multicenter real-world review of 10 kHz SCS outcomes for treatment of chronic trunk and/or limb pain.

Objectives: High-frequency spinal cord stimulation (HF-SCS) at 10 kHz has proven to be efficacious in the treatment of chronic back and leg pain in a randomized, controlled, trial (SENZA-RCT). However, large observational studies have yet to be published. Therefore, we performed a real-world, multicenter, retrospective, review of therapy efficacy in 1660 patients with chronic trunk and/or limb pain. Methods: Data were collected in a real-world environment and retrospectively sourced from a global database. Included patients were trialed and/or permanently implanted with HF-SCS at 10 kHz between April 2014 and January 2018. We evaluated responder rates at 3, 6, and 12 months post-implantation. Response was defined as ≥50% pain relief from baseline. A last visit analysis included responder rate along with overall change in function, sleep, quality of life, and medication intake versus baseline. Results: Eighty-four percent of our HF-SCS-treated patients had both chronic back and leg pain. At least 70% of patients reported response to therapy throughout 12 months of follow-up. This sustained responder rate was corroborated by the last visit value (74.1%). Most patients reported concomitant improvements in function (72.3%), sleep (68.0%), and quality of life (90.3%) at their last visit versus baseline. Thirty-two percent of patients reported decreased medication intake at their last visit. Interpretation: Sustained and effective pain relief was experienced by >70% of our HF-SCS-treated patients, consistent with the findings of a previously published randomized, controlled, trial. Our review provides complementary evidence to support the treatment of chronic back and leg pain with this therapy.

Deep brain stimulation for intractable neuropathic facial pain.

OBJECTIVE Deep brain stimulation (DBS) is a well-established, evidence-based therapy with FDA approval for Parkinson's disease and essential tremor. Despite the early successful use of DBS to target the sensory thalamus for intractable facial pain, subsequent studies pursuing various chronic pain syndromes reported variable efficacy, keeping DBS for pain as an investigational and "off-label" use. The authors report promising results for a contemporary series of patients with intractable facial pain who were treated with DBS. METHODS Pain outcomes for 7 consecutive patients with unilateral, intractable facial pain undergoing DBS of the ventral posteromedial nucleus of the thalamus (VPM) and the periaqueductal gray (PAG) were retrospectively reviewed. Pain was assessed preoperatively and at multiple postoperative time points using the visual analog scale (VAS), the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and the Pain Disability Index (PDI). RESULTS VAS scores significantly decreased from a mean ± SD of 9.0 ± 1.3 preoperatively to 2.6 ± 1.5 at 1 year postoperatively (p = 0.001). PDI scores decreased from a mean total of 48.5 to 28.5 (p = 0.01). SF-MPQ-2 scores decreased from a mean of 4.6 to 2.4 (p = 0.03). Notably, several patients did not experience maximum improvement until 6-9 months postoperatively, correlating with repeated programming adjustments. CONCLUSIONS DBS of the VPM and PAG is a potential therapeutic option for patients suffering from severe, intractable facial pain refractory to other interventions. Improved efficacy may be observed over time with close follow-up and active DBS programming adjustments.

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines.

INTRODUCTION: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice. METHODS: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain. RESULTS: The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations. CONCLUSION: New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery.

Percutaneous transoral clivoplasty and upper cervical vertebroplasties for multifocal skeletal lymphangiomatosis resulting in complete resolution of pain: case report.

Lymphangiomatosis is a rare congenital disorder that results in multiorgan system lymphatic invasion. Symptoms due to axial skeletal involvement can range from chronic bone pain to severe deformity resulting in radiculopathy, myelopathy, and even paralysis. The authors present a case of lymphangiomatosis of the clivus, C-1, and C-2, resulting in chronic pain. The patient was successfully treated with percutaneous transoral clivoplasty and vertebroplasty, without disease progression or return of symptoms at 2 years.

Peripheral Nerve Stimulation for Pain in Extremities: An Update.

Pain in extremities may occur in a variety of central and peripheral neuropathic and nociceptive syndromes, some of which may respond to central neuromodulation procedures. Peripheral neuromodulation techniques, either as a stand-alone therapy or as an adjuvant to spinal cord stimulation, may be particularly effective when the pain is localized to a part of a single extremity or when the source of the pain is related to the malfunction of a known peripheral nerve. Further, peripheral neuromodulation is used to treat disorders in which central simulation fails to provide discrete therapeutic paresthesia. Despite the fact that there are only a few neuromodulatory devices designed specifically for the periphery, clinical experiences are growing, and here we provide a clinical update on use of peripheral nerve stimulation (PNS) in management of chronic pain in extremities. Historical PNS strategies and innovative methods are reviewed and highlighted in this chapter. With the upcoming technological advances and new stimulation paradigms, along with clear updated guidelines statements, the utilization of PNS will likely continue to increase and improve the management of chronic pain syndromes in the extremities. The potential success of the novel devices specifically designed to target the peripheral nervous system is expected to positively impact and promote the use of PNS in treatment of chronic pain.

Treatment of medically refractory cancer pain with a combination of intrathecal neuromodulation and neurosurgical ablation: case series and literature review.

OBJECTIVE: Up to 90% of patients with advanced cancer experience intractable pain. For these patients, oral analgesics are the mainstay of therapy, often augmented with intrathecal drug delivery. Neurosurgical ablative procedures have become less commonly used, though their efficacy has been well-established. Unfortunately, little is known about the safety of ablation in the context of previous neuromodulation. Therefore, the aim of this study is to present the results from a case series in which patients were treated successfully with a combination of intrathecal neuromodulation and neurosurgical ablation. DESIGN: Retrospective case series and literature review. SETTING: Three institutions with active cancer pain management programs in the United States. METHODS: All patients who underwent both neuroablative and neuromodulatory procedures for cancer pain were surveyed using the visual analog scale prior to the first procedure, before and after a second procedure, and at long-term follow-up. Based on initial and subsequent presentation, patients underwent intrathecal morphine pump placement, cordotomy, or midline myelotomy. RESULTS: Five patients (2 male, 3 female) with medically intractable pain (initial VAS = 10) were included in the series. Four subjects were initially treated with intrathecal analgesic neuromodulation, and 1 with midline myelotomy. Each patient experienced recurrence of pain (VAS ≥ 9) following the initial procedure, and was therefore treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1; percutaneous radiofrequency cordotomy, N = 3), with significant long-term benefit (VAS 1-7). CONCLUSION: In cancer patients with medically intractable pain, intrathecal neuromodulation and neurosurgical ablation together may allow for more effective control of cancer pain.

Accuracy over space and time of computer-assisted fluoroscopic navigation in the lumbar spine in vivo.

OBJECTIVE: The integration of digital image-guided surgical navigation with C-arm fluoroscopy, known as virtual fluoroscopy (VF), has been shown to enhance the safety of spine surgery in vitro. Few clinical studies have assessed the accuracy of VF during actual spinal surgery, and no studies have investigated variations in accuracy over the course of a series of measurements obtained during operative cases. We sought to study the intraoperative accuracy of VF over time and space during lumbar pedicle screw placement in human patients. METHODS: Fluoroscopic images of the lumbar spine were obtained, calibrated, and saved to the Stealth Station (FluoroNav) on seven patients undergoing lumbar fusion surgery. The tracking arc was attached to an exposed lumbar spinous process, which was designated the index level. With use of anatomic surface irregularities in the laminae and spinous processes, several points were identified and registered on three different vertebrae directly adjacent to the index level vertebra. Every 15 minutes, throughout the operative case, the probe was brought to each point and the apparent distance from the original location recorded (as measured by the FluoroNav system). Measurements were collected from three vertebral levels adjacent to the index level over a time course of 120 minutes during the operation. RESULTS: At the index, index +1, index +2, and index +3 levels, 89%, 81%, 92%, and 64% of measurements were within <2 mm, whereas 97%, 96%, 97%, and 91% were within <3 mm, respectively. At 15, 30, 45, 60, 75, 90, 105, and 120 minutes, 96%, 89%, 85%, 61%, 85%, 90%, 93%, and 50% of measurements were within <2 mm, whereas 100%, 93%, 100%, 83%, 100%, 90%, 100%, and 100% of measurements were within <3 mm, respectively. The error in millimeters tended to increase as the distance from the index level increased (R = 0.19, P < 0.05) and as operative time increased (R = 0.26, P < 0.01). Calibration studies of intraoperative VF (IoVF) in the lumbar spine documented a reasonable degree of accuracy. The majority of sequential measurements obtained during IoVF in the lumbar spine were within an error range of <3 mm. CONCLUSIONS: Our results suggest that the use of VF is a reliable method of verifying the use of anatomic and/or radiographic landmarks for guidance during lumbar pedicle screw placement.

Frameless stereotactic image-guided C1-C2 transarticular screw fixation for atlantoaxial instability: review of 20 patients.

OBJECTIVE: We retrospectively studied 20 adults who underwent C1-C2 transarticular screw (TAS) fixation utilizing frameless stereotaxy. METHODS: The study group comprised 13 men and 7 women, with a mean age of 63 years (range 12-87 years). All patients demonstrated clinical and radiographic evidence of C1-C2 instability. The cause of the instability was trauma in 11 patients, rheumatoid arthritis in 6 patients, failed prior surgery in 2 patients, and congenital malformation in 1 patient. All patients underwent stabilization with C1-C2 TASs using image-guided frameless stereotaxy. RESULTS: There were no new or worsening neurologic symptoms reported at 18-month follow-up. Motor weakness improved in seven of nine patients, myelopathy in seven of seven, and gait in three of six patients in whom these deficits were present preoperatively. Postoperative complications included one surgical site abscess, one cutaneous pressure ulcer, and one iliac crest donor site infection. Of 36 screws placed, 33 (92%) were well positioned. Normal C1-C2 alignment was achieved in 17 of 20 (85%) patients. In 4 of 20 cases, screw implant, which was thought to be anatomically difficult, if not impossible, on the basis of routine magnetic resonance or computed tomography imaging, was actually accomplished successfully using surgical navigation. CONCLUSIONS: C1-C2 TAS placement is a safe and accurate surgical technique that may improve neurologic function. Use of intraoperative navigation can facilitate achieving difficult surgical trajectories that match the patient's anatomy, thus allowing TAS implant in patients who otherwise would not be candidates for this type of internal fixation.

Titanium cage-assisted polymethylmethacrylate reconstruction for cervical spinal metastasis: technical note.

OBJECTIVE: Reconstruction and stabilization of the cervical spine after vertebrectomy is an important goal in the surgical management of spinal metastasis. The authors describe their reconstruction technique using a titanium cage-Silastic tube construct injected with polymethylmethacrylate (PMMA) augmented by an anterior cervical plate. The surgical results using this technique are reviewed. METHODS: Six patients ranging from 43 to 70 years of age underwent resection of metastatic tumor in the cervical spine followed by cage-assisted PMMA reconstruction of the anterior spinal column. The following reconstruction technique was performed. A Silastic tube is incised longitudinally and placed circumferentially around a titanium cage with the opening facing anteriorly. The cage-Silastic tube construct is carefully tapped into the corpectomy defect and filled with PMMA. The final construct is then augmented with anterior cervical plate fixation. RESULTS: Two patients required additional posterior stabilization with lateral mass screws and rods. All patients achieved immediate stabilization, restoration of vertebral body height and normal lordosis, and preservation of the ability to walk independently. Five patients experienced significant palliation of biomechanical neck pain. There were no complications of neurological worsening, postoperative hematoma, wound infection, subsidence, graft dislodgement, or construct failure during a follow-up period of 1 to 19 months (mean, 6.8 mo). CONCLUSION: Titanium cage-assisted PMMA reconstruction augmented with an anterior cervical plate is an effective means of reconstruction after tumor resection in patients with cervical spinal metastasis. The Silastic tube holds the PMMA within the cage and protects the spinal cord from potential thermal injury.

Split spinal cord malformation in an elderly patient: case report.

Split spinal cord malformations (SCM) typically present in childhood and rarely in adulthood. Very little is known about the SCMs in the elderly, and the diagnosis can be easily missed. A 73-year-old woman with a childhood history of scoliosis and late ambulation milestones presented with a 2-year history of worsening low back pain and progressive difficulty walking. She had a mild gait disturbance with 4/5 weakness in left ankle dorsiflexion. Magnetic resonance imaging revealed a bifid spinal cord contained in a single thecal sac and a tethered cord with low-lying conus at L3. The patient was taken to the operating room and a soft-tissue median septum, as well as all other adhesions, was removed. The filum terminale was identified, coagulated, and divided. Six weeks later, the patient reported decreased back pain, improvement in ambulation, and markedly decreased used of narcotics for her back and leg pain. Her left ankle dorsiflexion strength improved to 4+/5. This patient had two hemicords encased in a single dural tube separated by a nonrigid, fibrous median septum and an associated tethered cord. Adult presentation of SCM is extremely rare. This case highlights the need to consider split cord malformation and tethered cord in the differential diagnosis not only for adults but also the elderly presenting with back pain, scoliosis, and difficulty walking.

Similarity in the fatigue behavior of trabecular bone across site and species.

Within the context of improving knowledge of the structure-function relations for trabecular bone for cyclic loading, we hypothesized that the S-N curve for cyclic compressive loading of trabecular bone, after accounting for differences in monotonic strength behavior, does not depend on either site or species. Thirty-five cores of fresh-frozen elderly human vertebral trabecular bone, harvested from nine donors (mean+/-S.D., age=74+/-17 years), were biomechanically tested in compression at sigma/E(0) values (ratio of applied stress to pre-fatigue elastic modulus) ranging from 0.0026 to 0.0070, and compared against literature data (J. Biomech. Eng. 120 (1998) 647-654) for young bovine tibial trabecular bone (n=37). As reported for the bovine bone, the number of cycles to failure for the human vertebral bone was related to sigma/E(0) by a power-law relation (r(2)=0.54, n=35). Quantitative comparison of these data against those reported for the bovine bone supported our hypothesis. Namely, when the differences in mean monotonic yield strain between the two types of bone were accounted for, a single S-N curve worked well for the pooled data (r(2)=0.75, n=72). Since elderly human vertebral and young bovine tibial trabecular bone represent two very different types of trabecular bone in terms of volume fraction and architecture, these findings suggest that the dominant failure mechanisms in trabecular bone for cyclic loading occur at the ultrastructural level.

General principles in the medical and surgical management of spinal infections: a multidisciplinary approach.

OBJECT: Infections along the spinal axis are characterized by an insidious onset, and the resulting delays in diagnosis are associated with serious neurological consequences and even death. Infections of the spine can affect the vertebral bodies, intervertebral discs, spinal canal, and surrounding soft tissues. Neurological dysfunction occurs when the spinal cord becomes compressed, edematous, or ischemic due to compression by abscess or vascular compromise. The aim of this paper was to detail general diagnostic and management principles for this disease. METHODS: Recent progress in medical technologies, including the development of potent antimicrobial drugs, advanced imaging, and improved surgical methods, have dramatically reduced morbidity and mortality rates for spinal infections; however, debate still exists on the proper management of this disease. In this paper, the authors review the current management protocols for spinal infections at their institution, focusing on medical and surgical treatments for vertebral osteomyelitis, intervertebral disc space infections, and spinal canal and soft-tissue abscesses. CONCLUSIONS: Technological advances in imaging modalities, pharmaceutics, and surgery have resulted in excellent outcomes and have greatly reduced the morbidity and mortality rates associated with spinal infections. Currently, treatment of spinal infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons. The key to successful management of spinal infections is early detection.

Quantitative computed tomography-based finite element models of the human lumbar vertebral body: effect of element size on stiffness, damage, and fracture strength predictions.

This study investigated the numerical convergence characteristics of specimen-specific "voxel-based" finite element models of 14 excised human cadaveric lumbar vertebral bodies (age: 37-87; M = 6, F = 8) that were generated automatically from clinical-type CT scans. With eventual clinical applications in mind, the ability of the model stiffness to predict the experimentally measured compressive fracture strength of the vertebral bodies was also assessed. The stiffness of "low"-resolution models (3 x 3 x 3 mm element size) was on average only 4% greater (p = 0.03) than for "high"-resolution models (1 x 1 x 1.5 mm) despite interspecimen variations that varied over four-fold. Damage predictions using low- vs high-resolution models were significantly different (p = 0.01) at loads corresponding to an overall strain of 0.5%. Both the high (r2 = 0.94) and low (r2 = 0.92) resolution model stiffness values were highly correlated with the experimentally measured ultimate strength values. Because vertebral stiffness variations in the population are much greater than those that arise from differences in voxel size, these results indicate that imaging resolution is not critical in cross-sectional studies of this parameter. However, longitudinal studies that seek to track more subtle changes in stiffness over time should account for the small but highly significant effects of voxel size. These results also demonstrate that an automated voxel-based finite element modeling technique may provide an excellent noninvasive assessment of vertebral strength.

Extensive intradural arachnoid cyst of the lumbar spinal canal: case report.

BACKGROUND: Spinal intradural arachnoid cysts are rare outpouchings of arachnoid lining occurring mainly in the thoracic and cervical regions. MRI is considered the diagnostic procedure of choice; however, some arachnoid cysts have been reported to elude diagnosis by MRI due to the similar signal intensity of the cyst and the subarachnoid space. CASE DESCRIPTION: We present a case of a 41-year-old woman with an intradural arachnoid cyst of the lumbar spinal canal. Diagnostic studies demonstrated a herniated L4-5 disk, which led to two operations. Despite intractable pain postoperatively, the MRI failed to reveal further focal compression of the nerve root. A myelogram suggested compression of the thecal sac by a dorsal mass lesion. The patient underwent a midline durotomy that revealed two large arachnoid cysts with the nerve roots beneath them pushed ventrally and to the right. Removal of the arachnoid layer resulted in complete fenestration of the cyst and allowed the nerve roots to freely float in the spinal fluid. CONCLUSION: In retrospect, the abnormality could be appreciated on multiple prior scans performed at another institution, demonstrating that in the patient with low back pain, degenerative disc disease is not the only diagnosis to consider.

Finite element modeling of the human thoracolumbar spine.

STUDY DESIGN: Biomechanical properties within cadaveric vertebral bodies were parametrically studied using finite element analysis after calibration to experimental data. OBJECTIVES: To develop and validate three-dimensional finite element models of the human thoracolumbar spine based on quantitative computed tomography scans. Specifically, combine finite element modeling together with biomechanical testing circumventing problems associated with direct measurements of shell properties. SUMMARY OF BACKGROUND DATA: Finite element methods can help to understand injury mechanisms and stress distribution patterns within vertebral bodies as an important part in clinical evaluation of spinal injuries. Because of complications in modeling the vertebral shell, it is not clear if quantitative computed tomography-based finite element models of the spine could accurately predict biomechanical properties. METHODS: We developed a novel finite element modeling technique based on quantitative computed tomography scans of 19 radiographically normal human vertebra bodies and mechanical property data from empirical studies on cylindrical trabecular bone specimens. Structural properties of the vertebral shell were recognized as parametric variables and were calibrated to provide agreement in whole vertebral body stiffness between model and experiment. The mean value of the shell properties thus obtained was used in all models to provide predictions of whole vertebral strength and stiffness. RESULTS: Calibration of n = 19 computer models to experimental stiffness yielded a mean effective modulus of the vertebral shell of 457 +/- 931 MPa ranging from 9 to 3216 MPa. No significant correlation was found between vertebral shell effective modulus and either the experimentally measured stiffness or the average trabecular modulus. Using the effective vertebral shell modulus for all 19 models, the predicted vertebral body stiffness was an excellent predictor of experimental measurements of both stiffness (r2= 0.81) and strength (r2 = 0.79). CONCLUSION: These findings indicate that modeling of the vertebral shell using a constant thickness of 0.35 mm and an effective modulus of 457 MPa, combined with quantitative computed tomography-based modeling of trabecular properties and vertebral geometry, can accurately predict whole vertebral biomechanical properties. Use of this modeling technique, therefore, should produce substantial insight into vertebral body biomechanical behavior and may ultimately improve clinical indications of fracture risk of this cohort.