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Radboud Universiteit Nijmegen, 2 juli 2013, Promotor : Verdonschot, N.J.J. Co-promotores : Homminga, J.J., Tanck, E.J.M., Contains fulltext : 112258.pdf (publisher's version ) (Open Access)

1 mei 2012, Item does not contain fulltext, One of the major problems facing the elderly spine is the occurrence of vertebral fractures due to low bone mass. Although typically attributed to osteoporosis, disc degeneration has also been suggested to play a role in vertebral fractures. Existing bone adaptation theories and simulations may explain the biomechanical pathway from a degenerated disc to an increased fracture risk. A finite element model of a lumbar segment was created and calibrated. Subsequently the disc properties were varied to represent either a healthy or degenerated disc and the resulting bone adaptation was simulated. Disc degeneration resulted in a shift of load from the nucleus to the annulus. The resulting bone adaptation led to a dramatically reduced density of the trabecular core and to an increased density in the vertebral walls. Degeneration of just the nucleus, and in particular the dehydration of the nucleus, resulted in most of this bone density change. Additional annulus degeneration had much less of an effect on the density values. The density decrease in the trabecular core as seen in this study matches clinical observations. Therefore, bone remodeling theories can assists in explaining the potential synergistic effects of disc degeneration and osteoporotis in the occurrence of vertebral fractures.

Contains fulltext : 96432.pdf (publisher's version ) (Closed access), STUDY DESIGN: In vitro biomechanical study. OBJECTIVE: To measure the effect that off-axis vertebral loading has on the stiffness and failure load of vertebrae. SUMMARY OF BACKGROUND DATA: Adjacent level vertebral fractures not only are common in patients who received a vertebroplasty treatment but also occur in patients with conservatively treated wedge fractures. The wedge-like deformity, which is present in both groups, changes the spinal alignment. The load of vertebrae adjacent to the fractured vertebra will change from perpendicular to the endplate to a more shearing, off-axis, load. This change may induce a higher fracture risk for vertebrae adjacent to wedge-like deformed vertebrae. METHODS: Twenty vertebrae, harvested from one osteopenic cadaver spine and three osteoporotic cadaver spines, were loaded until failure. The vertebrae were loaded either perpendicular to the upper endplate, representing vertebrae in a spine without wedge fractures (0 degrees group, n = 10), or at an angle of 20 degrees , representing vertebrae adjacent to a wedge fracture (20 degrees groups, n = 10). Vertebral failure load and stiffness were the most important outcome measures. RESULTS: The failure load was significantly higher (P 5 0.028) when tested at 0 degrees (2854 N, SD 5 622 N), compared with vertebrae tested at 20 degrees (2162 N, SD 5 670 N). Vertebrae were also significantly stiffer (P, 0.001) when tested at 0 degrees (4017 N/mm, SD 5 970 N/mm) than those tested at 20 degrees (2478 N/mm, SD 5 453 N/mm). CONCLUSION: The failure load of osteopenic/osteoporotic vertebrae was 24% lower under off-axis loads (20 degrees ) than under axial loads (0 degrees ). This study may lead to a better understanding of the etiology of adjacent vertebral fractures after wedge-like deformities and demonstrates the importance of height reconstruction of wedge fractures in order to normalize the loading conditions on adjacent vertebrae.

Item does not contain fulltext, Osteoporosis is a progressive systemic skeletal condition characterized by low bone mass and microarchitectural deterioration, with a consequent increase in susceptibility to fracture. Hence, osteoporosis would be best diagnosed by in vivo measurements of bone strength. As this is not clinically feasible, our goal is to estimate bone strength through the assessment of elastic properties, which are highly correlated to strength. Previously established relations between morphological parameters (volume fraction and fabric) and elastic constants could be applied to estimate cancellous bone stiffness in vivo. However, these relations were determined for normal cancellous bone. Cancellous bone from osteoporotic patients may require different relations. In this study we set out to answer two questions. First, can the elastic properties of osteoporotic cancellous bone be estimated from morphological parameters? Second, do the relations between morphological parameters and elastic constants, determined for normal bone, apply to osteoporotic bone as well? To answer these questions we used cancellous bone cubes from femoral heads of patients with (n=26) and without (n=32) hip fractures. The elastic properties of the cubes were determined using micro-finite element analysis, assuming equal tissue moduli for all specimens. The morphological parameters were determined using microcomputed tomography. Our results showed that, for equal tissue properties, the elastic properties of cancellous bone from fracture patients could indeed be estimated from morphological parameters. The morphology-based relations used to estimate the elastic properties of cancellous bone are not different for women with or without fractures.

Item does not contain fulltext, In this study, we investigate how morphological parameters and mechanical properties derived from microcomputed tomography (microCT) are affected by small errors in threshold value when variable bone structures and different bone volume fractions are involved. For this purpose, biopsies of vertebrae of 6-, 23-, and 230-week-old female pigs were scanned using microCT. For each specimen, five threshold values were determined within the range of thresholds that an observer could select realistically, in steps of 0.5%. The scans were converted to microfinite-element (microFE) models, used to determine the elastic moduli. A variation of 0.5% in threshold resulted in a 5% difference in bone volume fraction and 9% difference in maximal stiffness for bone cubes with a volume fraction of <0.15. When the volume fraction was >0.2, these differences were only 2% and 3%, respectively. For all bone cubes, the differences for trabecular thickness and bone surface density were <3%. The effects on morphological anisotropy and trabecular number were negligible for threshold variations of 0.5%. These findings suggest that threshold selection is important for the accurate determination of volume fraction and mechanical properties, especially for low bone volume fractions; the architectural directionality is less sensitive to changes in threshold.

Item does not contain fulltext, Osteoporosis is currently defined in terms of low bone mass. However, the source of fragility leading to fracture has not been adequately described. In particular, the contributions of bone tissue properties and architecture to the risk or incidence of fracture are poorly understood. In an earlier experimental study, it was found that the architectural anisotropy of cancellous bone from the femoral heads of fracture patients was significantly increased compared with age- and density-matched control material (Ciarelli et al., J Bone Miner Res 15:32-40; 2000). Using a combination of compression testing and micro-finite element analysis on a subset of cancellous bone specimens from that study, we calculated the hard tissue mechanical properties and the apparent (macroscopic) mechanical properties. The tissue modulus was 10.0 GPa (SD 2.2) for the control group and 10.8 GPa (SD 3.3) for the fracture group (not significant). There were no differences in either the apparent yield strains, percentages of highly strained tissue, or the relationship between apparent yield stress and apparent elastic modulus. Hence, a difference in the tissue yield properties is unlikely. At the apparent level, the fracture group had a significantly decreased transverse stiffness, resulting in increased mechanical anisotropy. These changes suggest that bone in the fracture group was "overadapted" to the primary load axis, at the cost of fragility in the transverse direction. We conclude that individuals with a history of osteoporotic fractures do not have weaker bone tissue. Architectural and mechanical anisotropy alone renders their bone weaker in the nonprimary loading direction.

Item does not contain fulltext, 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.

Item does not contain fulltext, In mature trabecular bone, both density and trabecular orientation are adapted to external mechanical loads. Few quantitative data are available on the development of architecture and mechanical adaptation in juvenile trabecular bone. We studied the hypothesis that a time lag occurs between the adaptation of trabecular density and the adaptation of trabecular architecture during development. To investigate this hypothesis we used ten female pigs at 6, 23, 56, 104, and 230 weeks of age. Three-dimensional morphological and mechanical parameters of trabecular bone samples from the vertebra and proximal tibia were studied using microcomputed tomography and micro-finite element analysis. Both bone volume fraction and stiffness increased rapidly in the initial growth phase (from 6 weeks on), whereas the morphological anisotropy started increasing only after 23 weeks of age. In addition, the anisotropy reached its highest value much later in the development than did bone volume fraction. Hence, the alignment of trabeculae was still progressing at the time of peak bone mass. Therefore, our hypothesis was supported by the time lag between the increase in trabecular density and the adaptation of the trabecular architecture. The rapid increase of bone volume fraction in the initial growth phase can be explained by the enormous weight increase of the pigs. The trabeculae aligned at later stages when the increase in weight, and thus the loading, was slowed considerably compared with the early growth stage. Hence, the trabecular architecture was more efficient in later years. We conclude that density is adapted to external load from the early phase of growth, whereas the trabecular architecture is adapted later in the development.

Item does not contain fulltext, STUDY DESIGN: A finite-element study to investigate the amount of trabecular bone at risk of fracture and the distribution of load between trabecular core and cortical shell, for healthy, osteopenic, and osteoporotic vertebrae. OBJECTIVES: To determine differences between healthy, osteopenic, and osteoporotic vertebrae with regard to the risk of fracture and the load distribution. SUMMARY OF BACKGROUND DATA: The literature contains no reports on the effects of osteopenia and osteoporosis on load distribution in vertebral bodies, nor any reports on the amount of trabecular bone at risk of fracture. METHODS: Computed tomography data of vertebral bodies were used to construct patient-specific finite-element models. These models were then used in finite-element analyses to determine the physiologic stresses and strains in the vertebrae. RESULTS: For all three classes of vertebrae the contribution of the trabecular core to the total load transfer decreased from about 70% near the endplates to about 50% in the midtransverse region. The amount of trabecular bone that is at risk of fracture was about 1% for healthy vertebrae, about 3% for osteopenic vertebrae, and about 16% for osteoporotic vertebrae. CONCLUSIONS: Our finite-element models indicated that neither osteopenia nor osteoporosis had any effect on the contribution of the trabecular core to the total load placed on the vertebra. The trabecular core carried about half the load. Our finite-element models indicated that osteoporosis had a significant effect on the amount of trabecular bone at risk of fracture, which increased from about 1% in healthy vertebrae to about 16% for osteoporotic vertebrae.

Item does not contain fulltext, The skeleton is continuously being renewed in the bone remodeling process. This prevents accumulation of damage and adapts the architecture to external loads. A side effect is a gradual decrease of bone mass, strength, and stiffness with age. We investigated the effects of bone loss on the load distribution and mechanical properties of cancellous bone using three-dimensional (3D) computer models. Several bone loss scenarios were simulated. Bone matrix was removed at locations of high strain, of low strain, and random throughout the architecture. Furthermore, resorption cavities and thinning of trabeculae were simulated. Removal of 7% of the bone mass at highly strained locations had deleterious effects on the mechanical properties, while up to 50% of the bone volume could be removed at locations of low strain. Thus, if remodeling would be initiated only at highly strained locations, where repair is likely needed, cancellous bone would be continuously at risk of fracture. Thinning of trabeculae resulted in relatively small decreases in stiffness; the same bone loss caused by resorption cavities caused large decreases in stiffness and high strain peaks at the bottom of the cavities. This explains that a reduction in the number and size of resorption cavities in antiresorptive drug treatment can result in large reductions in fracture risk, with small increases in bone mass. Strains in trabeculae surrounding a cavity increased by up to 1,000 microstrains, which could lead to bone apposition. These results give insight in the mechanical effects of bone remodeling and resorption at trabecular level.

Osteoporosis is characterized by low bone mass and an increased fracture risk. Measurements of bone mass alone, however, will not provide adequate information about the fracture risk, because the trabecular architecture or spatial distribution of the bone density has an important effect on the strength. We have developed a method to estimate the tissue strength of trabecular bone directly from 3D reconstructed axial CT-scans in combination with a finite element model. The method provides the stress distribution throughout the structure which can be used as a measure for the strength and fracture risk of the bone. A matter of concern with this method are the external loading conditions placed on the vertebral body, which might be strongly affected by the behavior of the intervertebral disk. In this study we have tested the effects of various intervertebral disk models on the load distribution through the vertebral body. A 3D model of a vertebral body was developed based on serial axial CT-scans which were converted to a 3D finite element model. The model was augmented with intervertebral disks at the upper and lower endplates. The disks contained a nucleus and an annulus region. The properties of the nucleus were varied to study the effects of a healthy disk with a functional nucleus pulposus and a degenerated disk with virtually no load bearing of the nucleus pulposus. The methods introduced in this study can be used to estimate load transfer through the vertebral body directly from CT-scans and, thereby, assessing the fracture risk of the bone and thus the status of osteoporosis