Three-dimensional multifractal analysis of trabecular bone under clinical computed tomography

Purpose: An adequate understanding of bone structural properties is critical for predicting fragility conditions caused by diseases such as osteoporosis, and in gauging the success of fracture prevention treatments. In this work we aim to develop multiresolution image analysis techniques to extrapolate high-resolution images predictive power to images taken in clinical conditions. Methods: We performed multifractal analysis (MFA) on a set of 17 ex vivo human vertebrae clinical CT scans. The vertebræ failure loads (FFailure) were experimentally measured. We combined bone mineral density (BMD) with different multifractal dimensions, and BMD with multiresolution statistics (e.g., skewness, kurtosis) of MFA curves, to obtain linear models to predict FFailure. Furthermore we obtained short- and long-term precisions from simulated in vivo scans, using a clinical CT scanner. Ground-truth data - high-resolution images - were obtained with a High-Resolution Peripheral Quantitative Computed Tomography (HRpQCT) scanner. Results: At the same level of detail, BMD combined with traditional multifractal descriptors (Lipschitz-Hölder exponents), and BMD with monofractal features showed similar prediction powers in predicting FFailure (87%, adj. R2). However, at different levels of details, the prediction power of BMD with multifractal features raises to 92% (adj. R2) of FFailure. Our main finding is that a simpler but slightly less accurate model, combining BMD and the skewness of the resulting multifractal curves, predicts 90% (adj. R2) of FFailure. Conclusions: Compared to monofractal and standard bone measures, multifractal analysis captured key insights in the conditions leading to FFailure. Instead of raw multifractal descriptors, the statistics of multifractal curves can be used in several other contexts, facilitating further research.Fil: Baravalle, Rodrigo Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Thomsen, Felix Sebastian Leo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur; ArgentinaFil: Delrieux, Claudio Augusto. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lu, Yongtao. Dalian University of Technology; ChinaFil: Gómez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; ArgentinaFil: Stošić, Borko. Universidade Federal Rural Pernambuco; BrasilFil: Stošić, Tatijana. Universidade Federal Rural Pernambuco; Brasi

RELATIONSHIPS OF LONG-TERM BISPHOSPHONATE TREATMENT WITH MEASURES OF BONE MICROARCHITECTURE AND MECHANICAL COMPETENCE

Oral bisphosphonate drug therapy is a common and effective treatment for osteoporosis. Little is known about the long-term effects of bisphosphonates on bone quality. This study examined the structural and mechanical properties of trabecular bone following 0-16 years of bisphosphonate treatment. Fifty-three iliac crest bone samples of Caucasian women diagnosed with low turnover osteoporosis were identified from the Kentucky Bone Registry. Forty-five were treated with oral bisphosphonates for 1 to 16 years while eight were treatment naive. A section of trabecular bone was chosen from a micro-computed tomography (Scanco µCT 40) scan of each sample for a uniaxial linearly elastic compression simulation using finite element analysis (ANSYS 14.0). Morphometric parameters (BV/TV, SMI, Tb.Sp., etc.) were computed using µCT. Apparent modulus, effective modulus and estimated failure stress were calculated. Biomechanical and morphometric parameters improved with treatment duration, peaked around 7 years, and then declined independently of age. The findings suggest a limit to the benefits associated with bisphosphonate treatment and that extended continuous bisphosphonate treatment does not continue to improve bone quality. Bone quality, and subsequently bone strength, may eventually regress to a state poorer than at the onset of treatment. Treatment duration limited to less than 7 years is recommended

Bone mechanical properties in healthy and diseased states

The mechanical properties of bone are fundamental to the ability of our skeletons to support movement and to provide protection to our vital organs. As such, deterioration in mechanical behavior with aging and/or diseases such as osteoporosis and diabetes can have profound consequences for individuals’ quality of life. This article reviews current knowledge of the basic mechanical behavior of bone at length scales ranging from hundreds of nanometers to tens of centimeters. We present the basic tenets of bone mechanics and connect them to some of the arcs of research that have brought the field to recent advances. We also discuss cortical bone, trabecular bone, and whole bones, as well as multiple aspects of material behavior, including elasticity, yield, fracture, fatigue, and damage. We describe the roles of bone quantity (e.g., density, porosity) and bone quality (e.g., cross-linking, protein composition), along with several avenues of future research.Author manuscrip

Updated trabecular bone score accounting for the soft tissue thickness (TBSTT) demonstrated significantly improved bone microstructure with denosumab in the FREEDOM TBS post hoc analysis

TBS algorithm has been updated to account for regional soft tissue noise. In postmenopausal women with osteoporosis, denosumab improved tissue thickness-adjusted TBS vs placebo independently of bone mineral density over 3 years, with the magnitude of changes from baseline or placebo numerically greater than body mass index-adjusted TBS. Introduction: To evaluate the effect of denosumab on bone microarchitecture assessed by trabecular bone score (TBS) in the FREEDOM study using the updated algorithm that accounts for regional soft tissue thickness (TBSTT) in dual-energy X-ray absorptiometry (DXA) images and to compare percent changes from baseline and placebo with classical body mass index (BMI)-adjusted TBS (TBSBMI). Methods: Postmenopausal women with lumbar spine or total hip bone mineral density (BMD) T score < - 2.5 and ≥ - 4.0 received placebo or denosumab 60 mg subcutaneously every 6 months. TBSBMI and TBSTT were assessed on lumbar spine DXA scans at baseline and months 1, 12, 24, and 36 in a subset of 279 women (129 placebo, 150 denosumab) who completed the 3-year FREEDOM DXA substudy and rolled over to open-label extension study. Results: Baseline characteristics were similar between groups. TBSTT in the denosumab group showed numerically greater changes from both baseline and placebo than TBSBMI at months 12, 24, and 36. Denosumab led to progressive increases in BMD (1.2, 5.6, 8.1, and 10.5%) and TBSTT (0.4, 2.3, 2.6, and 3.3%) from baseline to months 1, 12, 24, and 36, respectively. Both TBS changes were significant vs baseline and placebo from months 12 to 36 (p < 0.0001). As expected, BMD and TBSTT were poorly correlated both at baseline and for changes during treatment. Conclusion: In postmenopausal women with osteoporosis, denosumab significantly improved bone microstructure assessed by TBSTT over 3 years. TBSTT seemed more responsive to denosumab treatment than TBSBMI and was independent of BMD

HR‐pQCT measures of bone microarchitecture predict fracture : systematic review and meta‐analysis

HR‐pQCT is a non‐invasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (i) assess fracture‐associated differences in HR‐pQCT bone parameters and (ii) to determine if HR‐pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR‐pQCT (39/40 used XtremeCT scanners) to assess 1291‐3253 and 3389‐10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta‐analysis. An additional meta‐analysis of short‐term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture‐associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR‐pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from −2.6% (95% CI: −3.4 to −1.9) in radial cortical vBMD to −12.6% (95% CI: −15.0 to −10.3) in radial trabecular vBMD. Fracture‐associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR‐pQCT can predict incident fracture. Assessment of study quality, heterogeneity and publication biases verified the validity of these findings. Finally, we demonstrated that fracture‐associated deficits in total and trabecular vBMD, and certain tibial cortical parameters, can be reliably discerned from HR‐pQCT‐related precision error and can be used to detect fracture‐associated differences in individual patients. Although differences in other HR‐pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross‐sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR‐pQCT in clinical fracture prediction

Evaluation of the capability of the simulated dual energy X-ray absorptiometry-based two-dimensional finite element models for predicting vertebral failure loads

Prediction of the vertebral failure load is of great importance for the prevention and early treatment of bone fracture. However, an efficient and effective method for accurately predicting the failure load of vertebral bones is still lacking. The aim of the present study was to evaluate the capability of the simulated dual energy X-ray absorptiometry (DXA)-based finite element (FE) model for predicting vertebral failure loads. Thirteen dissected spinal segments (T11/T12/L1) were scanned using a HR-pQCT scanner and then were mechanically tested until failure. The subject-specific three-dimensional (3D) and two-dimensional (2D) FE models of T12 were generated from the HR-pQCT scanner and the simulated DXA images, respectively. Additionally, the areal bone mineral density (aBMD) and areal bone mineral content (aBMC) of T12 were calculated. The failure loads predicted by the simulated DXA-based 2D FE models were more moderately correlated with the experimental failure loads (R  = 0.66) than the aBMC (R  = 0.61) and aBMD (R  = 0.56). The 2D FE models were slightly outperformed by the HR-pQCT-based 3D FE models (R  = 0.71). The present study demonstrated that the simulated DXA-based 2D FE model has better capability for predicting the vertebral failure loads than the densitometric measurements but is outperformed by the 3D FE model. The 2D FE model is more suitable for clinical use due to the low radiation dose and low cost, but it remains to be validated by further in vitro and in vivo studies. [Abstract copyright: Copyright © 2019. Published by Elsevier Ltd.

Sex- and Age-Related Differences in Bone Microarchitecture in Men Relative to Women Assessed by High-Resolution Peripheral Quantitative Computed Tomography

The trabecular and cortical compartments of bone each contributes to bone strength. Until recently, assessment of trabecular and cortical microstructure has required a bone biopsy. Now, trabecular and cortical microstructure of peripheral bone sites can be determined noninvasively using high-resolution peripheral quantitative computed tomography (HR-pQCT). Studies that have used HR-pQCT to evaluate cohorts of both men and women have provided novel insights into the changes in bone microarchitecture that occur with age between the sexes, which may help to explain the lower fracture incidence in older men relative to women. This review will highlight observations from these studies on both the sex- and age-related differences in trabecular and cortical microstructure that may underlie the differences in bone strength, and thereby fracture risk, between men and women