Stochastic Assessment of Bone Fragility in Human Lumbar Spine

Osteoporotic fractures are a vital public health concern and create a great economic burden for our society. It is estimated that more than 2 million fractures occur in the United States at a cost of $17 billion each year. Deterioration of microarchitecture of trabecular bone is considered as a major contributor to bone fragility. Current clinical imaging modalities such as Dual-energy X-ray absorptiometry (DXA) are not able to describe bone microarchitecture due to their low resolution. The main objective of this study was to obtain the relationship between stochastic parameters calculated from bone mineral density (BMD) maps of DXA scans and the microarchitecture parameters measured from three dimensional (3D) images of human lumbar vertebrae acquired using a Micro-Computed Tomography (Micro-CT) scanner. Eighteen human lumbar vertebrae with intact posterior elements were scanned in the posterior-anterior projection using a DXA scanner. Stochastic parameters such as correlation length (L), sill variance (C) and nugget variance ( ) were calculated by fitting a theoretical model onto the experimental variogram of the BMD map of the human vertebrae. In addition, microarchitecture parameters such as bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), connectivity density (Conn.Dn), and bone surface-to-volume ratio (BS/BV) were measured from 3D images of the same human lumbar vertebrae. Significant correlations were observed between stochastic predictors and microarchitecture parameters of trabecular bone. Specifically, the sill variance was positively correlated with the bone volume fraction, trabecular thickness, trabecular number, connectivity density and negatively correlated with the bone surface to volume ratio and trabecular separation. This study demonstrates that stochastic assessment of the inhomogeneity of bone mineral density from routine clinical DXA scans of human lumbar vertebrae may have the potential to serve as a valuable clinical tool in enhancing the prediction of risks for osteoporotic fractures in the spine. The main advantage of using DXA scans is that it would be cost effective, since most hospitals already have DXA machines and there would be no need for purchasing new equipment

A New Method To Determine Volumetric Bone Mineral Density From Bi-Planar Dual Energy Radiographs Using A Finite Element Model: An Ex-Vivo Study

Finite element models (FEMs) derived from QCT-scans were developed to evaluate vertebral strength but QCT scanners limitations are restrictive for routine osteoporotic diagnosis. A new approach considers using bi-planar dual energy (BP2E) X-rays absorptiometry to build vertebral FEM. The purpose was to propose a FEM based on BP2E absorptiometry and to compare the vertebral strength predicted from this model to a QCT-based FEM. About 46 vertebrae were QCT scanned and imaged with BP2E X-rays. Subject-specific vertebral geometry and bone material properties were obtained from both medical imaging techniques to build FEM for each vertebra. Vertebral body volumetric bone mineral density (vBMD) distribution and vertebral strength prediction from the BP2E-based FEM and the QCT-based FEM were compared. A statistical error of 7[Formula: see text]mg/cm3 with a RMSE of 9.6% and a [Formula: see text] of 0.83 were found in the vBMD distribution differences between the BP2E-based and qCT-based FEM. The average vertebral strength was 3321[Formula: see text][Formula: see text] and 3768[Formula: see text][Formula: see text][Formula: see text for the qCT-based and BP2E-based FEM, respectively, with a RMSE of 641[Formula: see text]N and [Formula: see text] of 0.92. This method was developed to estimate vBMD distribution in lumbar vertebrae from a pair of 2D-BMD images and demonstrated to be accurate to personalize the mechanical properties in vitro

Analysis of PMMA distribution around spine cannulated pedicle screws in osteoporotic lumbar and sacral vertebrae

The main goal of this project has been to analyse the distribution of injected cement into vertebrae. The study has focused on the cement’s behaviour around pedicle screws inserted into lumbar (L4 and L5) and sacral (S1) vertebrae of elder people who underwent vertebroplasty. Models of the screw and cement were obtained from Computed Tomography. Once treated with CAD software, the models were ready to be studied. Longitudinal and transversal views of the maximum injected cement profiles were obtained. From these profiles, results could be obtained. They showed a tendency of injected cement into S1 vertebra to behave asymmetrically compared to a more symmetrical and homogeneous behaviour shown when injected into L4 and L5 vertebrae. Thus, leading to the assumption that pedicle screws injected into L4 and L5 vertebrae have a better chance of success than those injected into S1 vertebra

INFLUENCE OF POSTERIOR ELEMENTS ON THE CORRELATIONS BETWEEN MICROARCHITECTURE PARAMETERS OF TRABECULAR BONE AND STOCHASTIC PREDICTORS FROM THE DXA SCANS OF HUMAN LUMBAR VERTEBRAE

Osteoporosis is a bone disease affecting both postmenopausal women and older men. Bone fractures caused by osteoporosis are a major health concern, creating a great economic burden to our society. Bone mineral density (BMD), a measure of bone mass by Dual-energy X-ray Absorptiometry (DXA), is a major risk factor for bone fractures. In addition to BMD, trabecular microarchitecture also contributes to bone strength and therefore is a risk factor for osteoporotic fractures. Recently, stochastic predictors derived from DXA scans have been found to correlate with trabecular microarchitecture in human vertebrae. In routine clinical scans of the human lumbar spine, posterior elements are always included during the posterior-anterior (PA) projection of DXA scans. To our knowledge, the influence of posterior elements on the relationship between stochastic predictors and trabecular microarchitecture has not been investigated. Therefore, the objective of this study is to examine the effect of posterior elements on the estimation of stochastic predictors using simulated DXA scans. 3D MicroCT images of human vertebrae from the lumbar spine of five tissue donors were obtained. Simulated DXA images of human vertebrae with and without posterior elements were generated from these 3D MicroCT images. Stochastic parameters such as correlation length and sill variance were calculated by fitting a theoretical model onto the experimental variogram of simulated DXA images. Linear regression analyses were performed to examine the correlations between microarchitecture of trabecular bone and stochastic predictors from DXA images of human vertebrae with and without posterior elements. The sill variance of simulated DXA images without posterior elements was positively correlated with some of the microarchitecture parameters such as bone surface to volume ratio, trabecular separation, and negatively correlated with bone volume fraction, trabecular thickness, trabecular number. The sill variance of simulated DXA images of whole vertebrae was positively correlated with bone volume fraction, trabecular thickness, trabecular number, and connectivity density, and negatively correlated with the bone surface to volume ratio, trabecular separation. Although these correlations were not statistically significant, the correlations between the sill variance and microarchitecture parameters were mostly greater in the vertebral body without posterior elements than the whole vertebrae with intact posterior elements. The outcome of this study indicates that it is necessary to remove posterior elements from DXA scans of the lumbar spine to improve the prediction of bone fractures using stochastic predictors

Quantitative imaging techniques for the assessment of osteoporosis and sarcopenia

Bone and muscle are two deeply interconnected organs and a strong relationship between them exists in their development and maintenance. The peak of both bone and muscle mass is achieved in early adulthood, followed by a progressive decline after the age of 40. The increase in life expectancy in developed countries resulted in an increase of degenerative diseases affecting the musculoskeletal system. Osteoporosis and sarcopenia represent a major cause of morbidity and mortality in the elderly population and are associated with a significant increase in healthcare costs. Several imaging techniques are currently available for the non-invasive investigation of bone and muscle mass and quality. Conventional radiology, dual energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound often play a complementary role in the study of osteoporosis and sarcopenia, depicting different aspects of the same pathology. This paper presents the different imaging modalities currently used for the investigation of bone and muscle mass and quality in osteoporosis and sarcopenia with special emphasis on the clinical applications and limitations of each technique and with the intent to provide interesting insights into recent advances in the field of conventional imaging, novel high-resolution techniques and fracture risk

Advances in Clinical Application of Bone Mineral Density and Bone Turnover Markers

Bone mineral density is the main basis for the diagnosis of osteoporosis. The measurement methods of bone mineral density include dual X-ray absorptiometry (DXA), quantitative computer tomography (QCT), quantitative ultrasound (QUS), magnetic resonance imaging (MRI) and so on. Currently, bone mineral density measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis of osteoporosis. Bone turnover markers (BTMs) are biochemical products that reflect the activity of bone cells and the metabolic level of bone matrix, and they reflect the dynamic changes of bone tissue in the whole body earlier than bone mineral-density, procollagen type 1 N-terminal propeptide (PINP) and carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX) is sensitive BTMs, widely used in clinical practice, and can predict the occurrence of fractures. Some new markers such as Periostin, AGEs/RAGE, Gelsolin, and Annexin A2 provide new clues for exploring the mechanism of osteoporosis. The combination of the two can better carry out the diagnosis and differential diagnosis of multiple metabolic bone diseases, evaluate the therapeutic response of anti-osteoporotic medicines, and predict fracture risk

Comparative radiological anatomy of human, porcine and ovine vertebrae

Osteoporotic vertebral fractures represent an important health burden in the Western world, in particular given the aging population demographics of most Western countries. At present, the treatment options for osteoporotic vertebral fractures are limited, and often conservative, relying on medical pain management. Transpedicular spinal interventional techniques such as vertebroplasty and kyphoplasty offer a minimally invasive treatment option for osteoporotic vertebral fractures. However, there has been recent controversy regarding the efficacy of vertebroplasty for pain relief. Although these percutaneous techniques continue to be used and developed, there is no consensus on the pre-clinical testing of new instruments and cements. Human cadaveric vertebrae are expensive and of limited availability, and animal vertebrae offer a more easily accessible alternative, but there is no agreement within the literature as to which species best approximates the human. This thesis explores the currently available evidence comparing human and animal vertebrae, and performs comparison studies assessing basic morphometric measurements, bone texture, and statistical shape analysis, to decide upon the best animal model for the use in assessing novel transpedicular instruments and vertebral bone cements. The findings would also apply to developments in surgical transpedicular screws. The morphometry showed that sheep are generally closer to humans in the thoracic spine, whereas pigs are closer in the lumbar spine. Bone texture analysis demonstrated no significant differences in trabecular thickness between humans and either sheep or pigs. Statistical shape analysis corroborated the findings of basic morphometry. Taking the findings in combination, I would suggest that for the purposes of transpedicular techniques, the sheep is a closer model to the human in the thoracic spine, and the pig is closer in the lumbar spine

A shape analysis approach to prediction of bone stiffness using FEXI

The preferred method of assessing the risk of an osteoporosis related fracture is currently a measure of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). However, other factors contribute to the overall risk of fracture, including anatomical geometry and the spatial distribution of bone. Finite element analysis can be performed in both two and three dimensions, and predicts the deformation or induced stress when a load is applied to a structure (such as a bone) of defined material composition and shape. The simulation of a mechanical compression test provides a measure of whole bone stiffness (N mm−1). A simulation system was developed to study the sensitivity of BMD, 3D and 2D finite element analysis to variations in geometric parameters of a virtual proximal femur model. This study demonstrated that 3D FE and 2D FE (FEXI) were significantly more sensitive to the anatomical shape and composition of the proximal femur than conventional BMD. The simulation approach helped to analyse and understand how variations in geometric parameters affect the stiffness and hence strength of a bone susceptible to osteoporotic fracture. Originally, the FEXI technique modelled the femur as a thin plate model of an assumed constant depth for finite element analysis (FEA). A better prediction of tissue depth across the bone, based on its geometry, was required to provide a more accurate model for FEA. A shape template was developed for the proximal femur to provide this information for the 3D FE analysis. Geometric morphometric techniques were used to procure and analyse shape information from a set of CT scans of excised human femora. Generalized Procrustes Analysis and Thin Plate Splines were employed to analyse the data and generate a shape template for the proximal femur. 2D Offset and Depth maps generated from the training set data were then combined to model the three-dimensional shape of the bone. The template was used to predict the three-dimensional bone shape from a 2D image of the proximal femur procured through a DXA scan. The error in the predicted 3D shape was measured as the difference in predicted and actual depths at each pixel. The mean error in predicted depths was found to be 1.7mm compared to an average bone depth of 34mm. 3D FEXI analysis on the predicted 3D bone along with 2D FEXI for a stance loading condition and BMD measurement were performed based on 2D radiographic projections of the CT scans and compared to bone stiffness results obtained from finite element analysis of the original 3D CT scans. 3D FEXI provided a significantly higher correlation (R2 = 0.85) with conventional CT derived 3D finite element analysis than achieved with both BMD (R2 = 0.52) and 2D FEXI (R2 = 0.44)