dc.description.abstract
Osteoporosis is the most common bone disease, however, only 60% of patients with an increased fracture risk are correctly identified. Hereby, a major limitation is that mainly bone quantity (bone mass) is used for osteoporosis classification, where as bone quality (bone architecture and material properties) is usually neglected. While bone architecture has already been shown to be deteriorated in aging and osteoporosis, much less is known about potential changes of the material properties of trabecular bone tissue (individual trabeculae). Similarly, anti-resorptive drugs, used for osteoporosis treatment, have been shown to improve the mechanical properties of whole bones, but their effect on the material properties remains elusive. Further, a few previous studies supposed that glycation of trabecular bone (occurring naturally with aging or in diabetes) causes a decrease of tissue toughness, but the found effects were weak. In general, previous studies on micro-mechanical experiments of individual trabeculae were limited by testing only a small number of samples in different, not well-defined loading scenarios mainly in air, which cannot reflect the physiological tissue behavior. Taken together, there is a strong need to perform a thorough mechanical characterization of individual trabeculae. In the first part of this thesis a novel test set-up was developed to characterize individual trabeculae in defined monotonic, cyclic, and fatigue tensile tests in a wet environment at a high throughput rate. Further, a rheological model was applied to gain elastic, viscous, plastic, and failure properties of individual trabeculae in one single experiment. In the second part, these procedures were used to determine the effects of hydration,osteoporosis, anti-resorptive treatment, and glycation on the apparent mechanical and material properties. A key finding of the cyclic loading experiments was that trabecular bone tissue cannot be modeled properly as a linear-elastic material, as it demonstrates an elasto-visco-plastic behavior. Dehydration of individual bovine trabeculae indicated a 2-fold increase of tensile modulus and strength, accompanied with 3-fold decrease of toughness. As a consequence, previously determined material properties in air, that considered trabecular bone tissue as linear-elastic,are not reliable. Interestingly, apparent mechanical and material properties of individual human trabeculae from the femoral head were not significantly affected by osteoporosis or aging. In contrast, trabecular architecture was deteriorated in both conditions. Therefore, there is currently no need for computer simulations, such as Finite Element (FE) analysis, to adapt the input material properties due to aging or osteoporosis to predict fracture risk, at least in the femoral head. In contrast, anti-resorptive treatment of beagle dogs with alendronate (a bisphosphonate) resulted in a significantly larger tensile modulus and ultimate stress, associated with a significantly larger Tissue Mineral Density (TMD). Further, anti-resorptive treatment with raloxifene (a selective estrogen receptor modulator) caused a significantly larger toughness. Hence, improved whole bone mechanics is partially related to enhanced material properties, but the underlying mechanisms are distinct between different drugs. In vitro glycation of individual bovine trabeculae indicated an increased dynamic modulus and secant modulus. However, because of a limited sample size (15 in total), no final conclusions could be drawn so far. In conclusion, this thesis highlighted that trabecular bone tissue has to be modeled as an elasto-visco-plastic material. Hereby, the results reported in this thesis suggest that modeling of trabecular bone tissue in the human femoral head can be performed independently from aging or osteoporosis, such as in FE analysis for prediction of fracture risk. The improved whole bone mechanics after anti-resorptive treatment is at least partly caused by improved material properties. The presented findings will contribute to a better fracture risk prediction and a more profound understanding of the influence of bone quality on whole bone mechanics.
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