This study focussed on the reduced platen compression (RPC) testing of the cancellous bone of the proximal tibia. The objective of this study was to improve the current testing methods with an emphasis on the location of the RPC specimens, and to correlate the mechanical properties of the rodent cancellous bone with the various density measures. Analytical studies were made to assess the effect of the size and shape of the platen based on the values from mechanical testing of the cancellous bone. RPC specimens are made from transverse slices of the proximal tibia metaphysis. Specimen location was determined using planar radiograph method at a distance of 1.75 mm distal to the growth plate. The distance from the top of the proximal tibia to the line at 1.75 mm distal to the growth plate was measured and this distance is termed as the first cut distance. Specimen thickness of 2 mm was then cut for the RPC test. Endocortical method was followed to determine the platen sizing for RPC testing. The cancellous bone was then tested in compression to failure. Correlations were performed between the mechanical properties of the cancellous bone and the density measures from pQCT and radiographic techniques. SigmaStat and TableCurve 2D were used to perform the correlations and estimate the P value for the correlation. Linear and power law fits were made for all the correlations. Based on this study, several improvements to the reduced platen compression test were recommended. An improved specimen location method was developed. However, it requires a corrective distance to account for the tissue that cannot be identified in the radiographic analysis. A new method for estimating the density of the cancellous bone that is directly tested by the platen was developed. Correlations between the density of the cancellous bone and the mechanical properties show that, there is a strong correlation between ultimate stress and aluminum layer intensity. Elastic modulus correlates best with the last batch tested in this study. Recommendations for future study include advanced technology like finite element analysis and custom shaped platens to enhance RPC testing.

This thesis describes a study characterising some of the material properties of cancellous bone from patients suffering from either osteoporosis or osteoarthritis whose femoral heads were surgically removed during hip replacement operations. For comparison, a variety of animal bones, having a range of mineral contents, and synthetic hydroxyapatite were also studied. These material properties were studied using the following techniques: thermogravimetric analysis linked to mass spectrometer (TGA-MS), powder x-ray diffraction (PXRD), mercury intrusion porosimeter (MIP) and high-temperature x-ray diffraction (HTXRD). The animal bones used were deer antler, whale periotic fin, whale ear bone, whale tympanic bulla, cod clythrum and porpoise ear. The TGA-MS determined the organic and the mineral proportions in bone and within the mineral the amount of the different types of carbonate was identified and quantified. The PXRD was used to measure the lattice dimensions and the crystallite sizes of human bone in order to find out if these parameters are altered in diseased bone. In synthetic hydroxyaptite (SHA), the PXRD was employed to determine the optimum sintering temperature as well as for monitoring the phase change that occurred when SHA was heated to high temperature. Phase monitoring was further carried in two of the animal species using HTXRD. This was used in preference to post-sinter-quenching of samples in order to obtain true, <i>in-situ</i> measurements of the composition at each temperature.

No description available.

Cancellous bone constitutes much of the volume of bone which makes up axial skeletal sites such as the vertebrae of the spine and the femoral neck. However the increased vascularity of cancellous bone compared with cortical bone means that it is more prone to drug, endocrine and metabolic related effects and therefore these skeletal sites are more prone to the bone condition osteoporosis. With the bone condition osteoporosis increasing in prevalence it is becoming far more important not only for those at risk of having the condition to be diagnosed earlier, but also for the effects of the condition to be better understood. There is a need for the better clinical management of fractures and for therapies and medical practices that will best avoid the low trauma fractures that are seen as a consequence of the condition. This study is in two separate sections, the first constitutes an investigation into the diagnostic abilities of the CUBA Clinical and Sunlight Omnisense quantitative ultrasound systems; and on the other hand an examination of the osteoporotic risk factor questionnaires, Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-assessment Tool (OST), Patient Body Weight (pBW), Simple Calculated Osteoporosis Risk Estimation (SCORE) and the Study of Osteoporotic Fractures (SOFSURF). The skeletal status was assessed by DXA at the axial skeleton. The aim was to differentiate between the systems that could rationally be used to screen populations to identify those who needed DXA densitometry investigations, on the basis of ability. The second section of the study focused on the biomechanics of cancellous bone, with the initial studies examining the compressive properties of both osteoporotic and osteoarthritic cancellous bone and the effects that the conditions have on the compressive mechanics of the bone. The later section is the first ever study into the K, G and J-integral fracture mechanics of cancellous bone. It used osteoporotic and osteoarthritic cancellous bone from the femoral head of a cohort of ultrasound scanned patients and of some equine vertebral cancellous bone. The study focused on the identification of the dominant independent material variables which affected the compressive and fracture mechanics of cancellous bone, and the differences that were seen between the two different skeletal conditions. In addition to the independent variables, quantitative ultrasound (QUS) scans were performed on the donors of the femoral heads which enabled investigation into QUS’s ability to predict either the compressive or fracture mechanics of bone in-vivo. The study demonstrated that the investigation of the calcaneus using the CUBA clinical system provided the highest level of diagnostic accuracy (AUC: 0.755 - 0.95), followed by the questionnaires, of which the OSIRIS questionnaire was the best performer (AUC: 0.74 – 0.866), and lastly the Sunlight Omnisense results. The best option for the prediction of the lowest feasible DXA T-score was a combination of the CUBA Clinical results, the individual’s weight and the OSIRIS questionnaire (r2 = 45.5%), with potential minor, but significant, support also added by the OST and SOFSURF questionnaires (r2 = 46.8%). The compressive testing demonstrated that osteoporotic and osteoarthritic bone both performed differently with respect to the apparent density, with the osteoporotic bone adhering to the previously published power function relationships, but with the osteoarthritic bone having lower power functions. The stress intensity factor for plane strain testing (KQ or KC) and the critical strain energy release rate results were both influenced primarily by the apparent density with the K values obeying a power relationship to the power of 1.5 and G a relationship to the power 2. However, both the composition and integrity of the collagen network, (demonstrated by collagen cross-link analysis), played roles in the explanation of the fracture mechanics results. The J-integral results were distinctly different to those of the K and G results with regard to their dependence on composition and it is hypothesised that this is due to the structure of the bone having more dominant effects than the apparent density. In conclusion, the fracture mechanics of cancellous bone are contributed to by a complex combination of a number of variables, but with apparent density dominating the K and G fracture mechanics to a power function of between 1 and 2. Currently available QUS systems demonstrated an ability to relate to the Young’s modulus and strength but also, in this study, to the fracture mechanics variables of the cancellous bone from the hip. This relationship is a profound outcome which may help the clinical management of the condition and the fractures when they occur. The dependence on fracture mechanic variables points to a clear causal relationship between the bone fracture parameters and bone condition as underlying factors of osteoporotic fractures.

Cancellous bone constitutes much of the volume of bone which makes up axial skeletal sites such as the vertebrae of the spine and the femoral neck. However the increased vascularity of cancellous bone compared with cortical bone means that it is more prone to drug, endocrine and metabolic related effects and therefore these skeletal sites are more prone to the bone condition osteoporosis. With the bone condition osteoporosis increasing in prevalence it is becoming far more important not only for those at risk of having the condition to be diagnosed earlier, but also for the effects of the condition to be better understood. There is a need for the better clinical management of fractures and for therapies and medical practices that will best avoid the low trauma fractures that are seen as a consequence of the condition. This study is in two separate sections, the first constitutes an investigation into the diagnostic abilities of the CUBA Clinical and Sunlight Omnisense quantitative ultrasound systems; and on the other hand an examination of the osteoporotic risk factor questionnaires, Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Index of Risk (OSIRIS), Osteoporosis Self-assessment Tool (OST), Patient Body Weight (pBW), Simple Calculated Osteoporosis Risk Estimation (SCORE) and the Study of Osteoporotic Fractures (SOFSURF). The skeletal status was assessed by DXA at the axial skeleton. The aim was to differentiate between the systems that could rationally be used to screen populations to identify those who needed DXA densitometry investigations, on the basis of ability. The second section of the study focused on the biomechanics of cancellous bone, with the initial studies examining the compressive properties of both osteoporotic and osteoarthritic cancellous bone and the effects that the conditions have on the compressive mechanics of the bone. The later section is the first ever study into the K, G and J-integral fracture mechanics of cancellous bone. It used osteoporotic and osteoarthritic cancellous bone from the femoral head of a cohort of ultrasound scanned patients and of some equine vertebral cancellous bone. The study focused on the identification of the dominant independent material variables which affected the compressive and fracture mechanics of cancellous bone, and the differences that were seen between the two different skeletal conditions. In addition to the independent variables, quantitative ultrasound (QUS) scans were performed on the donors of the femoral heads which enabled investigation into QUS’s ability to predict either the compressive or fracture mechanics of bone in-vivo. The study demonstrated that the investigation of the calcaneus using the CUBA clinical system provided the highest level of diagnostic accuracy (AUC: 0.755 - 0.95), followed by the questionnaires, of which the OSIRIS questionnaire was the best performer (AUC: 0.74 – 0.866), and lastly the Sunlight Omnisense results. The best option for the prediction of the lowest feasible DXA T-score was a combination of the CUBA Clinical results, the individual’s weight and the OSIRIS questionnaire (r2 = 45.5%), with potential minor, but significant, support also added by the OST and SOFSURF questionnaires (r2 = 46.8%). The compressive testing demonstrated that osteoporotic and osteoarthritic bone both performed differently with respect to the apparent density, with the osteoporotic bone adhering to the previously published power function relationships, but with the osteoarthritic bone having lower power functions. The stress intensity factor for plane strain testing (KQ or KC) and the critical strain energy release rate results were both influenced primarily by the apparent density with the K values obeying a power relationship to the power of 1.5 and G a relationship to the power 2. However, both the composition and integrity of the collagen network, (demonstrated by collagen cross-link analysis), played roles in the explanation of the fracture mechanics results. The J-integral results were distinctly different to those of the K and G results with regard to their dependence on composition and it is hypothesised that this is due to the structure of the bone having more dominant effects than the apparent density. In conclusion, the fracture mechanics of cancellous bone are contributed to by a complex combination of a number of variables, but with apparent density dominating the K and G fracture mechanics to a power function of between 1 and 2. Currently available QUS systems demonstrated an ability to relate to the Young’s modulus and strength but also, in this study, to the fracture mechanics variables of the cancellous bone from the hip. This relationship is a profound outcome which may help the clinical management of the condition and the fractures when they occur. The dependence on fracture mechanic variables points to a clear causal relationship between the bone fracture parameters and bone condition as underlying factors of osteoporotic fractures.

Among vertebrates, whole-body movement is centered around the vertebral column. The bony vertebral column primarily consists of trabecular (spongy) bone that adapts in vivo to support mechanical demands respective to region, ontogeny, ecology, and locomotion. Previous work has extensively investigated the formfunction relationships of vertebral trabecular bone in terrestrial mammals, who use limb contact with a substrate as the primary support against gravity. However, we lack data from obligate swimming mammals whose locomotor ecology diverged from their terrestrial counterparts in two major ways: (1) body mass is supported by water’s uplifting buoyant forces and (2) swimmers power movement through dorsoventral loading of the axial body. This study examined vertebral trabecular bone mechanical properties and micoarchitecture from fully aquatic mammals, specifically sirenians (i.e. manatees) and cetaceans (i.e. dolphins and whales). We compression tested bone from several regions of the vertebral column among developmental stages in Florida manatees (Trichechus manatus latirostris) and among 10 cetacean species (Families Delphinidae and Kogiidae) with various swimming modes and diving behaviors. In addition, we microCT scanned a subset of cetacean vertebrae before subjecting them to mechanical tests. We demonstrated that in precocial manatee calves, vertebrae were the strongest and toughest in the posterior vertebral column, which may support rostrocaudal force propagation and increasing bending amplitudes towards the tail tip during undulatory swimming. Among cetaceans, we showed that greatest strength, stiffness, toughness, bone volume fraction, and degree of anisotropy were in rigidtorso shallow-divers, while properties had the smallest values in flexible-torso deep-divers. We propose that animals swimming in shallower waters actively swim more than species that conduct habitual glides during deep descents in the water column, and place comparatively greater loads on their vertebral columns. We found that cetacean bone volume fraction was the best predictor for mechanical properties. Due to the shared non-weight bearing conditions of water and microgravity, we present these data as a contribution to the body of work investigating bone adaptations in mammals that live in weightless conditions throughout life and evolutionary history. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

No description available.

The management of significant bone defects, delayed and non-union of fractures can be extremely challenging. Development of specific treatment is hindered by an absence of information regarding the molecular events which regulate these processes. In this thesis, a bilateral cancellous bone defect model of the femur and tibia was developed in a rodent and the spatiotemporal profile of TGF-β, BMP 2 and 7, Smads 1, 4 and 5 characterised. Next, the capability of acid solution to augment healing was tested in both a bone defect and in a closed femoral fracture model. Finally, a long term oestrogen deficiency (OVX) rat model of postmenopausal osteoporosis was characterised and the spatiotemporal profiles of IGF-1, IGFR-1, MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, BMP-2, BMP-4, BMP-7, TGF-β, Smad4, Smad7, VEGF, Flt-1, Ihh and FGF-2 were compared in femoral osteotomies between OVX and Sham groups. The bilateral cancellous defect model was successfully created with a number of advantages with which to recommend its use in future studies. TGF-β, BMP 2 and 7, Smads 1, 4 and 5 had characteristic spatiotemporal profiles during cancellous bone defect healing suggesting that they have a regulatory role. The results of the acid study were inconclusive and problems with substance delivery and maintenance at the desired site need to be addressed in the future to fully test this hypothesis. No significant differences were detected on histology or three-point mechanical testing between the fracture calluses of acid and control groups. In the final study, OVX rats after six months had significantly increased weight and decreased bone mineral density compared to their sham counterparts. A histological delay in osteotomy healing was observed in the OVX group but no significant differences on tensile testing were seen between OVX and Sham groups up to six weeks. Immunohistochemistry revealed that delayed healing may be due to the down-regulation of IGF-1, BMP-2, 4, and 7 and the up-regulation of MMP-3 in OVX compared to Sham groups. In conclusion, the results of this thesis give some insight into the molecular biology of bone defects and osteoporotic fractures. This information may also be useful in the development of specific treatments aimed at augmenting healing in bone defects and osteoporotic fractures.

The mechanical properties of the cancellous bone in the laboratory rat animal model are of great interest to the research community for the evaluation of treatments for osteoporosis. Cancellous bone responds rapidly and dramatically to disuse, various pathologies, nutritional deficiencies, and hormonal deficiencies and hence is often a primary focus in animal studies. Previous methods for evaluating the mechanical properties of cancellous bone in rat test specimens included both cortical and cancellous bone. This thesis introduces a new method to core cancellous specimens using a diamond wire saw in concert with specially designed fixtures. This method has been termed Isolated Cancellous Coring (ICC). The location and the geometry of the cored specimens were determined based on uCT analysis. The isolated cancellous specimens were subjected to uni-axial compression testing to evaluate the mechanical properties. Furthermore, the new method is evaluated by directly applying it to a study investigating the effects of estrogen replacement therapy in post-menopausal osteoporosis as simulated by the ovariectomized rat model. The results show that the ICC method can be applied to bone specimens with a large range in density and micro-architecture parameters. The compression testing of the isolated cancellous specimens provides a sensitive indicator of the effects of osteoporosis and treatment on the mechanical properties of the cancellous bone in the distal rat femur. Also, the results indicate a possible discordant relationship between bone mineral density and bone strength with respect to estrogen treatment. Power law regressions show that approximately 50% of the variation in ultimate strength can be accounted for with bone mineral density and the percent of bone volume per total volume.

Moderate energy restriction in young, exercising women attenuates the positive effects of exercise on bone density. Studies have shown that in the absence of adequate levels of circulating estrogen, there may not be enough functional estrogen receptor-a (ER-a) to respond adequately to loading. The experiment described in this document is significant because this model has not been explored under conditions of energy restriction (EnR) which are known to reduce circulating estrogen levels; it has been tested only in ovariectomized animals. The central hypothesis of this research is that reductions in estrogen due to EnR limit the ability of bone to respond to mechanical loading (LOAD) through a down-regulation of ER-a. Study one determined which nutrient’s (calcium or energy) restriction (-40 percent) had the greatest negative effects on the skeletal integrity of exercising female rats and whether exercise (EX) could mitigate these deleterious changes. EnR caused detrimental effects in many of the structural properties of bone; however EX attenuated losses in cancellous bone. Study two ascertained whether EX maintained cancellous bone mass in female rats subjected to graded EnR (-20 or -40 percent) and whether changes in endocrine factors were related. EX preserved cancellous bone volume and osteoblast activity under both levels of EnR, in addition to total body lean mass and bone mineral content. A similar maintenance of serum insulin-like growth factor and estradiol occurred in the EX EnR(40 percent) group suggesting that these changes may be related to the protective effects of EX. Study three determined the effects of 40 percent EnR on bone formation rate to LOAD in young adult female rats and tracked alterations in ovarian function (estradiol). Although higher than non-loaded animals, the response of bone to LOAD in EnR animals was dampened in comparison to energy-replete animals. The experiments described in this document are significant because these are the first experiments to explore the relationship between EnR and estrogen levels on cancellous bone response to LOAD. This is particularly important for physically active, energy restricted women because cancellous bone in these women will not experience the same effects of loading which can increase their risk for developing osteoporosis.