Alterations of bone microstructure and strength in end-stage renal failure

Summary: End-stage renal disease (ESRD) patients have a high risk of fractures. We evaluated bone microstructure and finite-element analysis-estimated strength and stiffness in patients with ESRD by high-resolution peripheral computed tomography. We observed an alteration of cortical and trabecular bone microstructure and of bone strength and stiffness in ESRD patients. Introduction: Fragility fractures are common in ESRD patients on dialysis. Alterations of bone microstructure contribute to skeletal fragility, independently of areal bone mineral density. Methods: We compared microstructure and finite-element analysis estimates of strength and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 33 ESRD patients on dialysis (17 females and 16 males; mean age, 47.0 ± 12.6years) and 33 age-matched healthy controls. Results: Dialyzed women had lower radius and tibia cortical density with higher radius cortical porosity and lower tibia cortical thickness, compared to controls. Radius trabecular number was lower with higher heterogeneity of the trabecular network. Male patients displayed only a lower radius cortical density. Radius and tibia cortical thickness correlated negatively with bone-specific alkaline phosphatase (BALP). Microstructure did not correlate with parathyroid hormone (PTH) levels. Cortical porosity correlated positively with "Kidney Disease: Improving Global Outcomes” working group PTH level categories (r = 0.36, p < 0.04). BMI correlated positively with trabecular number (r = 0.4, p < 0.02) and negatively with trabecular spacing (r = −0.37, p < 0.03) and trabecular network heterogeneity (r = −0.4, p < 0.02). Biomechanics positively correlated with BMI and negatively with BALP. Conclusion: Cortical and trabecular bone microstructure and calculated bone strength are altered in ESRD patients, predominantly in women. Bone microstructure and biomechanical assessment by HR-pQCT may be of major clinical relevance in the evaluation of bone fragility in ESRD patient

In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (

Biomechanical evaluation of different semi-rigid junctional fixation techniques using finite element analysis

BACKGROUND: Proximal junctional failure is a common complication attributed to the rigidity of long pedicle screw fixation constructs used for surgical correction of adult spinal deformity. Semi-rigid junctional fixation achieves a gradual transition in range of motion at the ends of spinal instrumentation, which could lead to reduced junctional stresses, and ultimately reduce the incidence of proximal junctional failure. This study investigates the biomechanical effect of different semi-rigid junctional fixation techniques in a T8-L3 finite element spine segment model.METHODS: First, degeneration of the intervertebral disc was successfully implemented by altering the height. Second, transverse process hooks, one- and two-level clamped tapes, and one- and two-level knotted tapes instrumented proximally to three-level pedicle screw fixation were validated against ex vivo range of motion data of a previous study. Finally, the posterior ligament complex forces and nucleus pulposus stresses were quantified.FINDINGS: Simulated range of motions demonstrated the fidelity of the general model and modelling of semi-rigid junctional fixation techniques. All semi-rigid junctional fixation techniques reduced the posterior ligament complex forces at the junctional zone compared to pedicle screw fixation. Transverse process hooks and knotted tapes reduced nucleus pulposus stresses, whereas clamped tapes increased nucleus pulposus stresses at the junctional zone.INTERPRETATION: The relationship between the range of motion transition and the reductions in posterior ligament complex and nucleus pulposus stresses was complex and dependent on the fixation techniques. Clinical trials are required to compare the effectiveness of semi-rigid junctional fixation techniques in terms of reducing proximal junctional failure incidence rates.</p

The Influence of Mineralization on Intratrabecular Stress and Strain Distribution in Developing Trabecular Bone

The load-transfer pathway in trabecular bone is largely determined by its architecture. However, the influence of variations in mineralization is not known. The goal of this study was to examine the influence of inhomogeneously distributed degrees of mineralization (DMB) on intratrabecular stresses and strains. Cubic mandibular condylar bone specimens from fetal and newborn pigs were used. Finite element models were constructed, in which the element tissue moduli were scaled to the local DMB. Disregarding the observed distribution of mineralization was associated with an overestimation of average equivalent strain and underestimation of von Mises equivalent stress. From the surface of trabecular elements towards their core the strain decreased irrespective of tissue stiffness distribution. This indicates that the trabecular elements were bent during the compression experiment. Inhomogeneously distributed tissue stiffness resulted in a low stress at the surface that increased towards the core. In contrast, disregarding this tissue stiffness distribution resulted in high stress at the surface which decreased towards the core. It was concluded that the increased DMB, together with concurring alterations in architecture, during development leads to a structure which is able to resist increasing loads without an increase in average deformation, which may lead to damage

Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach

Human cancers exhibit strong phenotypic differences that can be visualized noninvasively by medical imaging. Radiomics refers to the comprehensive quantification of tumour phenotypes by applying a large number of quantitative image features. Here we present a radiomic analysis of 440 features quantifying tumour image intensity, shape and texture, which are extracted from computed tomography data of 1,019 patients with lung or head-and-neck cancer. We find that a large number of radiomic features have prognostic power in independent data sets of lung and head-and-neck cancer patients, many of which were not identified as significant before. Radiogenomics analysis reveals that a prognostic radiomic signature, capturing intratumour heterogeneity, is associated with underlying gene-expression patterns. These data suggest that radiomics identifies a general prognostic phenotype existing in both lung and head-and-neck cancer. This may have a clinical impact as imaging is routinely used in clinical practice, providing an unprecedented opportunity to improve decision-support in cancer treatment at low cost

The Feasibility of High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) in Patients with Suspected Scaphoid Fractures

Introduction: Diagnosing scaphoid fractures remains challenging. High-resolution peripheral quantitative computed tomography (HR-pQCT) might be a potential imaging technique, but no data are available on its feasibility to scan the scaphoid bone in vivo. Methodology: Patients (≥18 years) with a clinically suspected scaphoid fracture received an HR-pQCT scan of the scaphoid bone (three 10.2-mm stacks, 61-μm voxel size) with their wrist immobilized with a cast. Scan quality assessment and bone contouring were performed using methods originally developed for HR-pQCT scans of radius and tibia. The contouring algorithm was applied on coarse hand-drawn pre-contours of the scaphoid bone, and the resulting contours (AUTO) were manually corrected (sAUTO) when visually deviating from bone margins. Standard morphologic analyses were performed on the AUTO- and sAUTO-contoured bones. Results: Ninety-one patients were scanned. Two out of the first five scans were repeated due to poor scan quality (40%) based on standard quality assessment during scanning, which decreased to three out of the next 86 scans (3.5%) when using an additional thumb cast. Nevertheless, after excluding one scan with an incompletely scanned scaphoid bone, post hoc grading revealed a poor quality in 14.9% of the stacks and 32.9% of the scans in the remaining 85 patients. After excluding two scans with contouring problems due to scan quality, bone indices obtained by AUTO- and sAUTO-contouring were compared in 83 scans. All AUTO-contours were manually corrected, resulting in significant but small differences in densitometric and trabecular indices (<1.0%). Conclusions: In vivo HR-pQCT scanning of the scaphoid bone is feasible in patients with a clinically suspected scaphoid fracture when using a cast with thumb part. The proportion of poor-quality stacks is similar to radius scans, and AUTO-contouring appears appropriate in good- and poor-quality scans. Thus, HR-pQCT may be promising for diagnosis of and microarchitectural evaluations in suspected scaphoid fractures

Long-term functional outcome of distal radius fractures is associated with early post-fracture bone stiffness of the fracture region:An HR-pQCT exploratory study

\u3cp\u3eIdentifying determinants of long-term functional outcome after a distal radius fracture is challenging. Previously, we reported on the association between early HR-pQCT measurements and clinical outcome 12 weeks after a conservatively treated distal radius fracture. We extended the follow-up and assessed functional outcome after two years in relation to early HR-pQCT derived bone parameters. HR-pQCT scans of the fracture region were performed in 15 postmenopausal women with a distal radius fracture at 1-2 (baseline), 3-4 weeks and 26 months post-fracture. Additionally, the contralateral distal radius was scanned at baseline. Bone density, micro-architecture parameters and bone stiffness using micro-finite element analysis (μFEA) were evaluated. During all visits, wrist pain and function were assessed using the patient-rated wrist evaluation questionnaire (PRWE), quantifying functional outcome with a score between 0 and 100. Two-year PRWE was associated with torsional and bending stiffness 3-4 weeks post-fracture (R2: 0.49, p = 0.006 and R2: 0.54, p = 0.003, respectively). In contrast, early micro-architecture parameters of the fracture region or contralateral bone parameters did not show any association with long-term outcome. This exploratory study indicates that HR-pQCT with μFEA performed within four weeks after a distal radius fracture captures biomechanical fracture characteristics that are associated with long-term functional outcome and therefore could be a valuable early outcome measure in clinical trials and clinical practice.\u3c/p\u3