Bert van Rietbergen

Finite Element Analysis Based on In Vivo HR-pQCT Images of the Distal Radius Is Associated With Wrist Fracture in Postmenopausal Women

BMD, bone microarchitecture, and bone mechanical properties assessed in vivo by finite element analysis were associated with wrist fracture in postmenopausal women.

Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in postmenopausal women

Assessment of bone strength at the radius by micro-finite element analysis (muFEA) has already been associated with wrist fractures. In this study, the analysis has been extended to the distal tibia, and to a larger group of subjects to examine the association with several types of fragility fractures. We have compared muFEA based on in vivo HR-pQCT measurements of BMD and microarchitecture at the radius and tibia, in a case-control study involving 101 women with prevalent fragility fracture and 101 age-matched controls, from the OFELY cohort. Areal BMD was measured by DXA at the radius and the hip. All parameters were analyzed in a principal component (PC) analysis (PCA), and associations between PCs and fractures were computed as odds ratios (OR [95% CI]) per SD change. Radius (tibia) PCA revealed three independent components explaining 76% (77%) of the total variability of bone characteristics. The first PC describing bone strength and quantity, explained 50% (46%) of variance with an OR=1.84 [1.27-2.67] (2.92 [1.73-4.93]). The second PC including trabecular microarchitecture, explained 16% (10%) of variance, with OR=1.29 [0.90-1.87] (1.11 [0.82-1.52]). The third PC related to load distribution explained 10% (20%) of variance, with OR=1.54 [1.06-2.24] (1.32 [0.89-1.96]). Moreover, at the radius, vertebral fractures were associated with trabecular microarchitecture PC with OR=1.86 [1.14-3.03], whereas nonvertebral fractures were associated with bone strength and quantity PC with OR=2.03 [1.36-3.02]. At the tibia, both vertebral (OR=2.92 [1.61-5.28]) and nonvertebral fracture (2.64 [1.63-4.27]) were associated to bone strength and quantity PC. In conclusion, muFEA parameters at the radius and tibia were associated with all types of fragility fractures. We have also shown that muFEA parameters obtained with distal tibia data were associated with prevalent fractures with a similar magnitude that with parameters obtained at the radius.

Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in men

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Mens Bones (STRAMBO) cohort.

Combination of topological parameters and bone volume fraction better predicts the mechanical properties of trabecular bone

Trabecular bone structure may complement bone volume/total volume fraction (BV/TV) in the prediction of the mechanical properties. Nonetheless, the direct in vivo use of information pertaining to trabecular bone structure necessitates some predictive analytical model linking structure measures to mechanical properties. In this context, the purpose of this study was to combine BV/TV and topological parameters so as to better estimate the mechanical properties of trabecular bone. Thirteen trabecular bone mid-sagittal sections were imaged by magnetic resonance (MR) imaging at the resolution of 117 x 117x 300 microm(3). Topological parameters were evaluated in applying the 3D-line skeleton graph analysis (LSGA) technique to the binary MR images. The same images were used to estimate the elastic moduli by finite element analysis (FEA). In addition to the mid-sagittal section, two cylindrical samples were cored from each vertebra along vertical and horizontal directions. Monotonic compression tests were applied to these samples to measure both vertical and horizontal ultimate stresses. BV/TV was found as a strong predictor of the mechanical properties, accounting for 89-94% of the variability of the elastic moduli and for 69-86% of the variability of the ultimate stresses. Topological parameters and BV/TV were combined following two analytical formulations, based on: (1) the normalization of the topological parameters; and on (2) an exponential fit-model. The normalized parameters accounted for 96-98% of the variability of the elastic moduli, and the exponential model accounted for 80-95% of the variability of the ultimate stresses. Such formulations could potentially be used to increase the prediction of the mechanical properties of trabecular bone.

Computational finite element bone mechanics accurately predicts mechanical competence in the human radius of an elderly population

High-resolution peripheral quantitative computed tomography (HR-pQCT) is clinically available today and provides a non-invasive measure of 3D bone geometry and micro-architecture with unprecedented detail. In combination with microarchitectural finite element (μFE) models it can be used to determine bone strength using a strain-based failure criterion. Yet, images from only a relatively small part of the radius are acquired and it is not known whether the region recommended for clinical measurements does predict forearm fracture load best. Furthermore, it is questionable whether the currently used failure criterion is optimal because of improvements in image resolution, changes in the clinically measured volume of interest, and because the failure criterion depends on the amount of bone present. Hence, we hypothesized that bone strength estimates would improve by measuring a region closer to the subchondral plate, and by defining a failure criterion that would be independent of the measured volume of interest. To answer our hypotheses, 20% of the distal forearm length from 100 cadaveric but intact human forearms was measured using HR-pQCT. μFE bone strength was analyzed for different subvolumes, as well as for the entire 20% of the distal radius length. Specifically, failure criteria were developed that provided accurate estimates of bone strength as assessed experimentally. It was shown that distal volumes were better in predicting bone strength than more proximal ones. Clinically speaking, this would argue to move the volume of interest for the HR-pQCT measurements even more distally than currently recommended by the manufacturer. Furthermore, new parameter settings using the strain-based failure criterion are presented providing better accuracy for bone strength estimates.

Introduction and evaluation of a gray-value voxel conversion technique.

In micro finite element analyses (microFEA) of cancellous bone, the 3D-imaging data that the FEA-models are based on, contain a range of gray-values. In the construction of the eventual FEA-model, these gray-values are commonly thresholded. Although thresholding is successful at small voxel sizes, at larger voxel sizes there is substantial loss of trabecular connectivity. We propose a new method: the gray-value method, where the microFEA-models use the information within the 3D-imaging data directly, without prior thresholding. Our question was twofold. First, how does the gray-value method compare to both plain and mass-compensated thresholding? Second, what is the effect of element size on the results obtained with the gray-value method? We used nine microCT-scans of human vertebral cancellous bone. These were degraded to represent different resolutions, and converted into microFEA-models using plain thresholding, mass-compensated thresholding, and the gray-value method. The apparent elastic moduli of the specimens were determined using microFEA. The different methods were compared on the basis of the apparent elastic moduli, compared to those calculated for a 28 microm reference model. The results showed that the gray-value method greatly improves the results relative to other methods. The gray-value method gives accurate predictions of the apparent elastic moduli, for voxel sizes up to one trabecular thickness (Tb.Th.). For voxel sizes greater than one Tb.Th. the accuracy, although still better than for both thresholding methods, becomes increasingly worse.

Remodeling of fracture callus in mice is consistent with mechanical loading and bone remodeling theory

During the remodeling phase of fracture healing in mice, the callus gradually transforms into a double cortex, which thereafter merges into one cortex. In large animals, a double cortex normally does not form. We investigated whether these patterns of remodeling of the fracture callus in mice can be explained by mechanical loading. Morphologies of fractures after 21, 28, and 42 days of healing were determined from an in vivo mid‐diaphyseal femoral osteotomy healing experiment in mice. Bone density distributions from microCT at 21 days were converted into adaptive finite element models. To assess the effect of loading mode on bone remodeling, a well‐established remodeling algorithm was used to examine the effect of axial force or bending moment on bone structure. All simulations predicted that under axial loading, the callus remodeled to form a single cortex. When a bending moment was applied, dual concentric cortices developed in all simulations, corresponding well to the progression of remodeling observed experimentally and resulting in quantitatively comparable callus areas of woven and lamellar bone. Effects of biological differences between species or other reasons cannot be excluded, but this study demonstrates how a difference in loading mode could explain the differences between the remodeling phase in small rodents and larger mammals.

Bone morphology allows estimation of loading history in a murine model of bone adaptation.

Bone adapts its morphology (density/micro- architecture) in response to the local loading conditions in such a way that a uniform tissue loading is achieved (‘Wolff’s law’). This paradigm has been used as a basis for bone remodeling simulations to predict the formation and adaptation of trabecular bone. However, in order to predict bone architectural changes in patients, the physiological external loading conditions, to which the bone was adapted, need to be determined. In the present study, we developed a novel bone loading estimation method to predict such external loading conditions by calculating the loading history that produces the most uniform bone tissue loading. We applied this method to murine caudal vertebrae of two groups that were in vivo loaded by either 0 or 8 N, respectively. Plausible load cases were sequentially applied to micro-finite element models of the mice vertebrae, and scaling factors were calculated for each load case to derive the most uniform tissue strain-energy density when all scaled load cases are applied simultaneously. The bone loading estimation method was able to predict the difference in loading history of the two groups and the correct load magnitude for the loaded group. This result suggests that the bone loading history can be estimated from its morphology and that such a method could be useful for predicting the loading history for bone remodeling studies or at sites where measurements are difficult, as in bone in vivo or fossil bones.

Effects of vibration treatment on tibial bone of ovariectomized rats analyzed by in vivo micro-CT.

Daily low‐amplitude, high‐frequency whole‐body vibration (WBV) treatment can increase bone formation rates and bone volume in rodents. Its effects vary, however, with vibration characteristics and study design, and effects on 3D bone microstructure of ovariectomized animals over time have not been documented. Our goal was to determine the effects of WBV on tibial bone of ovariectomized, mature rats over time using an in vivo micro‐CT scanner. Adult rats were divided into: ovariectomy (OVX) (n = 8), SHAM‐OVX (n = 8), OVX and WBV treatment (n = 7). Eight weeks after OVX, rats in the vibration group were placed on a vibrating platform for 20 min at 0.3 g and 90 Hertz. This was done 5 days a week for six weeks, twice a day. Zero, 8, 10, 12 and 14 weeks after OVX, in vivo micro‐CT scans were made (vivaCT 40, Scanco Medical AG) of the proximal and diaphyseal tibia. After sacrifice, all tibiae were dissected and tested in three‐point bending. In the metaphysis between 8 to 12 weeks after OVX, WBV treatment did not alter structural parameters compared to the OVX group and both groups continued to show deterioration of bone structure. In the epiphysis, structural parameters were not altered. WBV also did not affect cortical bone and its bending properties. To summarize, no substantial effects of 6 weeks of low‐magnitude, high‐frequency vibration treatment on tibial bone microstructure and strength in ovariectomized rats were found.

Challenges in longitudinal measurements with HR-pQCT: Evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

Definition of identical regions between repeated computed tomography (CT) scans is a key factor to monitor changes in bone microarchitecture. In longitudinal studies, accurate determination of the volume of interest (VOI), using three dimensional (3D) registration may improve precision. Therefore, the aim of our study was to investigate the short-term reproducibility of bone geometry, density, microstructure and biomechanical parameters assessed by HR-pQCT and micro-finite element (μFE) derived analyses, using the cross-sectional area (CSA) registration method in comparison with the use of 3D registration, to find overlapping regions between scans. Fifteen healthy individuals (aged 21-47 years) underwent 3 separate scans at the distal radius and tibia, within a one-month interval. Reproducibility was assessed after double contouring the cortical compartment and after applying three different methods to determine the common region between repeated scans: (i) the VOI was determined with no registration, i.e., on 110 slices, (ii) the VOI was determined after CSA-based registration, and (iii) the VOI was determined after 3D registration. Both pre- and post-registration short-term reproducibility for each subject was determined. With no registration, CVrms of geometry parameters ranged from 0.5 to 3.7%, showing a slight variation in the CSA between scans. When the CSA registration method was employed, the variability of geometry (CVrms<1.8%) and density parameters (CVrms<1.8%), was better than that obtained without registration. By removing the effect of repositioning, the 3D registration further improved the reproducibility of cortical bone measurements compared to other methods. Indeed, significant improvements were found for cortical geometry and microstructure measurements (CVrms ranged from 0.4% to 10.7% at both sites; p<0.05), whereas the impact on trabecular bone measurements was restricted to its geometry parameter. The repositioning error was significantly reduced, most markedly at the radius compared to the tibia. For μFE measures, the impact of 3D registration on whole bone stiffness was negligible, indicating adequate assessment of longitudinal changes in estimated biomechanical properties, even without registration. In conclusion, we have shown that the 3D registration improved the identification of the common region retained for longitudinal analysis, contributing to improve the reproducibility of cortical bone parameter measurements. We also quantified the minimally detectable bone changes to help designing future studies with HR-pQCT.