Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on Jan. 19, 2010). Includes bibliographical references.

Thesis (M.S.)--University of Missouri-Columbia, 2004. / Typescript. Vita. Includes bibliographical references (leaves 83-94). Also available on the Internet.

There is an increasing interest in evaluating the role of ultrasound in the identification and management of osteoporosis. We may measure the velocity of ultrasound through bone and the frequency-dependent attenuation, generally referred to as broadband ultrasound attenuation (BUA). The dependence of these parameters upon osteoporotic changes in density and architecture(total loss or thinning of trabeculae width) is still not well defined. A physical model for cancellous bone was developed by introducing an array of cylindrical voids of defined diameter and configuration into polymethylmethacrylate (Perspex). Experimental studies on the cancellous bone model demonstrated that the relationship between BUA and porosity is approximately parabolic, with low BUA values obtained at both low (cortical bone) and high (bone marrow) porosities. This explains the discrepancies in the correlation between BUA and density for different bone structures reported in the literature. BUA was also found to be dependent on the number of pores and the pore distribution(structure). Velocity was found to be dependent on pore size only. BUA and velocity were also found to be temperature dependent. Permeability provides quantitative information related to structure, validated using the perspex model. In vitro studies were carried out on bovine and human cancellous bone (calcaneus and vertebrae). The relationship between Young's modulus, strength and density followed the power law predicted by theoretical models. Measurements on bovine and vertebrae samples were carried out in three orthogonal directions. Young's modulus, strength, BUA, velocity and permeability were shown to be direction dependent and hence dependent upon structure. The relationship between BUA and density followed the parabolic trend observed in the physical model, with the human samples on the rising phase and the bovine on the falling phase of the parabola. BUA in the calcaneus was found to follow a power law relationship with density (BUA = rho[1.99]). BUA was a goodpredictor of strength in both the bovine (R[2] = 74%) and calcaneus (R[2] = 75%) samples. Velocity was a good predictor of both Young's modulus and strength whenapplied to the bar wave equation (E = V[2]rho) with an R[2] of 94% and 88% respectively for the calcaneus and 91% and 92% respectively for the bovine samples. For thecalcaneus samples an R[2] of 83% and 80% for Young's modulus and strength were obtained when density in the bar wave equation was substituted by BUA. The cortical end plates have a significant offset effect on BUA in the calcaneus. Permeability was highly correlated to strength. BUA and velocity were shown to be good predictors of cancellous bone strength in vitro. Future work should concentrate upon the investigation of controlled structural models of cancellous bone and also on the extrapolation of this study to the in vivo prediction of bone strength.

Thesis (M.S.M.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / OBJECTIVE: Prior studies examining the association of warfarin use and osteoporotic fractures have found conflicting results and have had methodological problems, such as confounding by indication and confounding by duration of warfarin use. Thus, we studied the association of warfarin use with fractures at the hip, spine and wrist, among older men and women with atrial fibrillation recruited from the general population, using rigorous statistical tools to overcome challenges faced by prior studies. METHODS: We included men and women ≥65 years with incident atrial fibrillation, without history of fracture, followed between 2000-2010 from The Health Improvement Network (THIN). Long-term warfarin use was defined in two ways: 1) warfarin use ≥ 1year; 2) warfarin use ≥3 years. Non-use was defined as no use of warfarin over the follow-up period. Propensity scores (PS) for warfarin use were calculated using logistic regression with long-term use of warfarin as the dependent variable and age, sex, body mass index (BMI), history of multiple falls, deep venous thrombosis, pulmonary embolism, heart failure, neuropsychiatric impairment, hyperthyroidism, estrogen use, beta blockers, corticosteroids, bisphosphonates, smoking and alcoholism as independent variables. Each warfarin user was then matched by PS to a non-user by the “greedy matching” method. Incidence rates were calculated for warfarin users and non-users. The association between long-term warfarin use and risk of hip, spine and wrist fractures was evaluated using Cox-proportional hazards models. RESULTS: Incidence rates of hip fracture were 5.21 and 6.20 per 1000 person-years among subjects with warfarin use >1 (n=20,346) and >3 (n=11,238) years, respectively. The hazard ratios of hip fracture for warfarin use >1 and >3 years were 1.08 (95% CI 0.87, 1.35) and 1.13 (95% CI: 0.84, 1.5), respectively. Similar findings were observed between warfarin use and risk of spine or wrist fracture. CONCLUSIONS: Long-term use of warfarin among older adults with atrial fibrillation is not associated with increased risk of osteoporotic fractures and thus, does not necessitate additional surveillance or prophylaxis. / 2031-01-01

No description available.

Made available in DSpace on 2015-09-17T15:24:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-12-16. Added 1 bitstream(s) on 2015-09-17T15:47:11Z : No. of bitstreams: 1 000846999.pdf: 3202334 bytes, checksum: 42c4628c71bee25da9831c39ef405651 (MD5) / O objetivo deste estudo foi avaliar o reparo ósseo na interface osso/implante em ratas com osteoporose induzida. As ratas submetidas à ovariectomia bilateral foram alimentadas com uma dieta pobre em cálcio. Dois grupos receberam tratamento medicamentoso (raloxifeno [OVX RAL] ou alendronato [OVX ALE]) e outro grupo não recebeu nenhuma medicação (OVX ST). O grupo controle foi submetido à cirurgia fictícia e foi alimentado com uma dieta normal (SHAM DN). Cada animal recebeu um implante em cada tíbia. Os animais foram eutanasiados após 14 ou 42 dias. Foram realizadas as análises biomecânica (torque reverso), extensão linear de contato osso/implante (ELCOI) e dinâmica óssea periimplantar pela proporção dos fluorocromos calceína/alizarina, aplicando-se a análise de variância ANOVA e o pós-teste de Tukey (p<0,05). A imunoistoquímica marcou a precipitação de osteoprotegerina (OPG), RANKL, TRAP e osteocalcina (OC). O medicamento RAL melhorou o reparo ósseo periimplantar, em que o grupo ALE foi semelhante ao grupo OVX ST. Não houve diferenças estatisticamente significativas no torque reverso (p = 0,861), na precipitação dos fluorocromos (calceína/alizarina) e na ELCOI entre os grupos OVX RAL e grupo controle - SHAM DN (p > 0,05). As imunomarcações de OPG e RANKL foram similares para os grupos RAL e SHAM; houve moderada expressão de OC aos 14 dias. A TRAP foi marcada intensamente aos 42 dias para o grupo OVX. Portanto, o raloxifeno melhorou o reparo ósseo periimplantar de ratas osteoporóticas, sugerindo a sua indicação no tratamento da osteoporose. / The aim of this study was to evaluate the bone healing in bone/implant interface in rats with induced osteoporosis. The rats underwent bilateral ovariectomy were fed a diet low in calcium. Two groups received drug treatment (raloxifene [OVX RAL] or alendronate [OVX ALE]) and the other group received no medication (OVX NT). The control group underwent sham surgery and was fed a normal diet (SHAM ND). Each animal received an implant on the tibia. The animals were euthanized after 14 or 42 days. The biomechanical analysis (reverse torque), linear extension contact bone / implant (BIC) and bone dynamics periimplantar by the proportion of fluorochrome calcein/alizarin, applying the ANOVA and Tukey's post-test (p<0.05). Immunohistochemistry marked precipitation of osteoprotegerin (OPG), RANKL, TRAP and osteocalcin (OC). The RAL improved drug peri-implant bone repair, wherein the ALE OVX group was similar to the ST group. There were no statistically significant differences in reverse torque (p = 0.861), precipitation of fluorochromes (calcein/alizarin) and BIC between OVX RAL and control groups - SHAM ND (p> 0.05). The immunostaining of OPG and RANKL were similar to RAL and SHAM groups; there was moderate OC expression at 14 days. TRAP was marked intensely at 42 days for the OVX group. Therefore, raloxifene improved peri-implant bone repair of osteoporotic rats, suggesting its indication in the treatment of osteoporosis.

Osteoporosis is a common complication of many autoimmune diseases that is typically attributed to disease specific factors rather than a direct autoimmune process. This thesis arises from the investigation of a patient with severe high bone turnover osteoporosis who was identified as having autoimmune disease but whose osteoporosis deteriorated despite appropriate treatment. This presentation led to the hypothesis that neutralising autoantibodies to the bone protective cytokine osteoprotegerin (OPG) may have developed. Serum from the index patient, but not healthy controls, was able to immunoprecipitate recombinant OPG protein, demonstrating that OPG had become the target of an autoimmune response. Purified immunoglobulins from the index case were able to inhibit the function of OPG in vitro, by suppressing OPG-mediated inhibition of a luciferase reporter cell line. This represents the first description of disease associated with neutralising antibodies to OPG. Whilst the immunoprecipitation assay did identify OPG antibodies in further patients these results were difficult to quantify. A more robust enzyme linked immunosorbent assay for OPG antibodies was developed using OPG as a capture antigen, which allowed the screening of patient cohorts. Presence of OPG antibodies was defined as a titre greater than the mean plus three standard deviations of 101 healthy volunteers. A low prevalence of 14/864 (1.6%) was seen in a general population cohort and no association with bone density or turnover was seen. An association with higher vascular calcification score in this cohort requires replication. A prevalence of 37/315 (11.7%) was seen in an osteoporosis cohort though no association was seen with bone density or response to treatment. In a coeliac cohort OPG antibodies were identified in 14/282 (5.0%) patients and presence of antibody was independently associated with reduced spine bone density. Functional inhibition of OPG was shown in vitro in 3/14 (21.4%) of the positive cases. Case finding of osteoporosis in the coeliac cohort was not improved by identification of OPG antibodies. These results are consistent with OPG antibodies being pathological in a small number of patients with osteoporosis but a clinical utility of measuring OPG antibodies has not been established.

Resumo: É cada vez maior a parcela de pessoas idosas na população brasileira e com este fenômeno o número de pessoas afetadas por patologias crônico-degenerativas. Dentre estas uma doença que merece destaque é a osteoporose, uma vez que vem se tornando um problema de saúde pública. Um dos principais fatores de risco para osteoporose é a deficiência estrogênica, sendo assim este estudo objetivou avaliar o efeito da deficiência estrogênica no tecido ósseo durante um período de 360 dias através de análise radiográfica e biomecânica. Para tanto 80 ratas, com 3 meses de idade e peso de aproximadamente 250g, foram divididas em 10 grupos experimentais (n=8) de acordo com o tempo de sacrifício e cirurgia a que foram submetidas (ovariectomia e cirurgia sham). As ratas pertencentes aos grupos OVZ e SHAM tiveram sua ração controlada (30g por animal). Após o período determinado (30, 60, 90, 180 e 360 dias das cirurgias) as ratas foram pesadas, anestesiadas e sacrificadas e seus fêmures retirados para análise. Os dados obtidos foram submetidos ao teste estatístico ANOVA e Tukey, com nível de significância de 5%. De acordo com os resultados obtidos observou-se que nos períodos de 30, 60 e 90 dias os efeitos da deficiência estrogênica sobre o tecido ósseo foram significativos / Abstract: The Brazilian population has undergone a process of aging, and this phenomenon with the number of people affected by chronic diseases is increasing. Among these a disease that deserves mention is osteoporosis, since it has become a public health problem. One of the main risk factors for osteoporosis is estrogen deficiency, so to better understand how estrogen deficiency affects the bone tissue present study aimed to evaluate the effect of estrogen deficiency on bone tissue over a period of 360 days by radiographic and biomechanics analysis. For this purpose 80 rats, 3 months old and weighing about 250g were divided into 10 groups (n = 8) according to the time of sacrifice and who underwent surgery (ovariectomy and sham surgery). The rats belonging to groups OVZ and SHAM had controlled his diet (30g per animal). After the specified period (30, 60, 90, 180 and 360 days of surgery) the rats were weighed, anesthetized and sacrificed, and their femurs were removed for analysis. Data were submitted to ANOVA and Tukey tests with significance level of 5%. According to the results obtained showed that in periods of 30, 60 and 90 days the effects of estrogen deficiency on bone tissue were significant / Orientador: Rosilene Fernandes da Rocha / Coorientador: Luana Marotta Reis de Vasconcellos / Banca: Juliana Madureira de Souza Lima Alonso / Banca: Mari Eli Leonelli de Moraes / Mestre

Orientador: Solange Maria de Almeida / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-10T00:43:38Z (GMT). No. of bitstreams: 1 Freitas_DeborahQueirozde_D.pdf: 863530 bytes, checksum: bf09329a36f133306020d488b7ecaa3c (MD5) Previous issue date: 2007 / Resumo: A osteoporose e a irradiação são fatores que interferem no processo de reparação óssea e podem ocorrer simultaneamente, especialmente em mulheres idosas. Atualmente, várias substâncias, conhecidas como radioprotetores, têm sido estudadas, pois minimizam os efeitos deletérios da radiação; dentre eles, pode-se citar o selênio. O objetivo desse trabalho foi avaliar o efeito radioprotetor do selenito de sódio no processo de reparo ósseo em ratas ovariectomizadas submetidas à irradiação. Para isso, oitenta ratas foram submetidas à ovariectomia e divididas em quatro grupos: ovariectomizado, ovariectomizado/selênio, ovariectomizado/irradiado e ovariectomizado/selênio/irradiado. Quarenta dias após, um defeito ósseo foi confeccionado nas tíbias dos animais. Dois dias após essa cirurgia, os animais dos grupos ovariectomizado/selênio eovariectomizado/selênio/irradiado receberam 0,8 mg Se/Kg de peso corpóreo. No dia seguinte, apenas os animais pertencentes aos grupos ovariectomizado/irradiado e ovariectomizado/selênio/irradiado receberam 10 Gy de radiação X na região dos membros inferiores. Os animais foram sacrificados 7, 14, 21 e 28 dias após a cirurgia. O processo de reparação óssea foi avaliado por análise morfológica, utilizando-se a coloração pelo Tricrômico de Masson, e por análise do número de trabéculas ósseas e da birrefrigência (coloração pelo Picrosírius). Pela análise morfológica, foi possível observar um atraso no processo de reparo ósseo nos animais do grupo ovariectomizado/irradiado e similaridade entre os grupos ovariectomizado, ovariectomizado/selênio e ovariectomizado/selênio/irradiado, o que demonstrou o efeito radioprotetor do selênio sem toxicidade / Abstract: Osteoporosis and ionizing radiation affect the bone healing and people can suffer both conditions, especially older women. At the moment, antioxidant radioprotectors have been evaluated, such selenium compounds. This study aimed at evaluating the selenium protection in the bone repair process in ovariectomized rats submitted to an irradiation procedure. For this purpose, eighty ovariectomized female Wistar rats were randomly divided in four experimental groups: ovariectomized, ovariectomized/selenium, ovariectomizedlirradiated and ovariectomized/selenium/irradiated. Abone defect was made on all animals' tibias forty days after ovariectomy. Two days after surgery, only ovariectomized/selenium and ovariectomized/seleniumlirradiated rats received 0.8 mg Se/Kg. Three days after surgery, only ovariectomized irradiated and ovariectomized/selenium/irradiated rats received 10 Gy of X rays on the lower limbs region. The animals were sacrificed 7, 14, 21 and 28 days after surgery in order to assess the repair process, which was evaluated by morphologic analysis in Masson Tricromic. lt was also evaluated by analysis of trabecular bone number in Masson Tricromic and birefringence analysis in Picrosirius. It was possible to observe a delay in the bone repair process in the irradiated/ovariectomized group and similarity between ovariectomized, ovariectomized/selenium and ovariectomized/selenium/irradiated, which proved the selenium radioprotection without its toxicity / Doutorado / Radiologia Odontologica / Doutor em Radiologia Odontológica

Abstract Bisphosphonates (BPs) are used in the treatment of osteoporosis. However, their effects, especially long-term effects, on bone and bone healing are not fully known. Clodronate (dichloromethylene bisphosphonic acid) is a first-generation BP. The thesis was based on two animal experiments. The first, with 199 rats on long-term clodronate treatment, was divided into four separate substudies. The effects of long-term administration of clodronate to rats were investigated after 32 weeks of treatment. The effects on the femoral shaft, femoral neck and vertebra in normal, non-osteoporotic skeleton were described in two publications. The evaluations were made by biomechanical, densitometric, histological, hematological and electron-microscopic investigations. Fracture healing was investigated in rats after 24 weeks of clodronate treatment. The tibia was fractured, and the effects of treatments were evaluated at 4 and 8 weeks after the fracture. Radiographs and densitometric pQCT in the evaluation of experimental fracture healing were compared. In the other experiment with 30 mice, a mouse immobilisation osteoporosis model for further studies was investigated. Long-term administration of clodronate at therapeutic dosage had no harmful impacts but rather some beneficial effects on normal, non-osteoporotic bone. However, long-term high-dose clodronate treatment resulted in a decrement of tibial length but did not have any other significant or adverse effects. In the evaluation of fracture healing, pQCT proved to be better than radiographs in differentiating the total mineralised cross-sectional area of callus and the area of compact bone. Clodronate treatment does not seem to prolong the fracture healing process, even when administered on a long-term basis before the fracture. Clodronate increased the size of callus, but had only a minor effect on its biomechanical properties. Three weeks of hind limb immobilization caused local osteopenia in the tibia when compared to its contralateral leg. In conclusion, this thesis suggests that long-term administration of clodronate at therapeutic dosage has no harmful, but rather some beneficial effects on normal, non-osteoporotic bone. However, a fivefold dose of clodronate causes a slight decrease in the growth of tibial length. Healing of fractures during or after clodronate treatment is not inhibited.