Indiana University-Purdue University Indianapolis (IUPUI) / Chronic kidney disease (CKD) results in an increased fracture risk, partially due to elevations in parathyroid hormone (PTH) that lead to substantial bone loss. On its own, bone loss does not explain bone fragility in CKD, suggesting that changes in skeletal tissue (bone quality) may also be present. Understanding the factors that lead to fracture in these patients will have a substantial impact on patient care and could lead to a better understanding of how to reduce their fracture risk. Due to their suppression of PTH, calcitriol and its analogues are the current standard of care for bone disease in CKD. Yet, surprisingly little is known of their effects on bone. Agents effective in treating osteoporosis are not recommended in advanced CKD due to the lack of data regarding their efficacy and safety in these patients. The goals of the current study were to determine (1) the impact of CKD on bone quality, (2) the ability of calcitriol to improve skeletal parameters, and (3) the efficacy of various pharmacological interventions (calcium, bisphosphonates, anti-sclerostin antibody, and raloxifene) on bone mass, quality, and mechanical properties in CKD bone disease. Using a slowly progressive rat model of CKD, renal and mineral metabolism, bone morphology, bone quality, and bone mechanics (at several length scales) were assessed. Primarily due to elevated PTH, mechanical testing and tissue-level assessments revealed compromised bone quantity (high cortical porosity and low trabecular volume) and quality (high collagen cross-linking and low matrix bound water). Despite clinically relevant reductions in PTH, calcitriol treatment had no positive impact on skeletal properties. Most agents were only effective when PTH levels were normal. Raloxifene, however, led to greater whole bone and material toughness (the ability of bone to tolerate existing damage) despite modest PTH suppression. While the examination of bone quality in CKD is still in its infancy, these results indicate that enhancing bone quality with raloxifene may be an effective means to compensate for bone loss in CKD.

Indiana University-Purdue University Indianapolis (IUPUI) / Skeletal fractures due to bone disease impact an estimated 1.5 million Americans per year, creating a large economic burden on our society. Treatment of bone diseases prior to fracture often involves bisphosphonates (current gold-standard in osteoporosis care and prevention). Although bisphosphonates decrease fracture incidence, they often improve bone mass without regard for bone quality. Thus, although bisphosphonates increase the amount of bone present, the inherent bone material strength often decreases, creating a trade-off that increases the risk of atypical fractures after long-term use. This trade-off demonstrates the need for a treatment that targets both bone quality AND quantity. Although bone quality is important, the components of bone that contribute to bone quality are incompletely understood, making it difficult to create new pharmacological agents. With this in mind, my particular area of interest is in understanding how mechanical stimuli protects the formation of bone, leading to improved bone quality. Initially, this area was explored through use of tibial loading in a disease mouse model (osteolathyrism, induced by injection of beta-aminoproprionitrile) as a means of assessing how the body is able to compensate for decreased bone quality. The results of the BAPN and tibial loading studies indicated that injecting mice with BAPN may not be the ideal method to induce osteolathyrism. However, other intriguing results from the BAPN studies then led us into an exploration of how tibial loading itself contributes to bone quality.

No description available.

<p dir="ltr">Investigating the deformation and failure of human cortical bone under altered hydration contributes to the understanding of bone fracture. Further, studying the impact of hydration on bone deformation can lead to developing fracture prevention strategies that will enhance the lives of the aging population. In addition, characterization of cortical bone water modulation effects on biomechanical behavior helps us understand how bone dynamically changes due to aging, health conditions, and therapeutic interventions.</p><p dir="ltr">The concepts in this thesis are demonstrated on bone specimens of a 75-year-old male human subject. To investigate the potential role of water in bone as modulated by selective estrogen receptor modulators, we used magnetic resonance imaging to characterize bound water in human samples. The behavior of human cortical bone under mechanical loading protocols was tested to analyze the bone failure surface. Bone microstructure, microdamage, and fractures were observed from progressive bending experiments. Earlier evidence suggests that treating human cortical bone with Raloxifene (RAL) toughens bone but does not affect strength.</p><p dir="ltr">Questions remain about how RAL treatment affects bone biomechanics with the consideration of size effects. In this research, experiments were conducted on samples mimicking the thickness of cortical bone. Smaller thickness samples investigated in prior work were also considered, and intrinsic strength and tissue damage were introduced. Additionally, ultra-short echo-time magnetic resonance images were employed to observe 3D spatial information of bound and free water in the bone.</p><p dir="ltr">This research seeks to combine methods in bone biology and the mechanics of materials to solve problems of bone fragility. Linear strength concepts do not distinguish between treatments. However, treatment effects are detected with a nonlinear approach. Furthermore, this study provides valuable insights into quantifying bound water content within in-vitro specimen samples. These findings pave the way for further research into continued advancements addressing skeletal health challenges.</p>

No description available.

Este experimento foi realizado com o objetivo de avaliar a redução dos níveis de cálcio e fósforo disponível em dietas suplementadas com doses crescentes de fitase para frangos de corte. Foram utilizados pintinhos machos da linhagem Cobb (n = 1152) distribuídos em um delineamento inteiramente casualizado em esquema fatorial 3 x4 (três níveis de cálcio e fósforo disponível e quatro níveis de fitase) com 12 tratamentos e oito repetições de 12 aves cada. Os tratamentos experimentais foram: T1 Dieta com níveis de cálcio e fósforo disponível de acordo com o proposto por Rostagno et al. (2011) para as diferentes fases; T2 Dieta com 90% dos níveis de cálcio e fósforo disponível proposto por Rostagno et al. (2011) para as diferentes fases; T3 Dieta com 80% dos níveis cálcio e fósforo disponível proposto por Rostagno et al. (2011) para as diferentes fases; T4 Dieta do T1 + fitase 500 FTU/Kg de ração; T5 Dieta do T2 + fitase 500 FTU/Kg de ração; T6 Dieta do T3 + fitase 500 FTU/Kg de ração; T7 Dieta do T1 + fitase 1.000 FTU/Kg de ração; T8 Dieta do T2 + fitase 1.000 FTU/Kg de ração; T9 Dieta do T3 + fitase 1.000 FTU/Kg de ração; T10 Dieta do T1 + fitase 1.500 FTU/Kg de ração; T11 Dieta do T2 + fitase 1.500 FTU/Kg de ração; T12 Dieta do T3 + fitase 1.500 FTU/Kg de ração. As dietas foram a base de milho e farelo de soja. As aves foram pesadas aos 7, 21 e 42 dias de idade. As características de desempenho foram avaliadas e, aos 42 dias de idade, foram avaliados o rendimento de carcaça e os cortes comerciais. O estudo da qualidade óssea, como a análise da densidade e resistência da tíbia, também foi realizado. Com o aumento das inclusões de fitase houve aumento linear de ganho de peso médio aos 7 dias e aos 21 dias. Da mesma forma, houve redução linear na conversão alimentar aos 21 dias, com o aumento dos níveis de fitase. Considerando o período de 1 a 42 dias, a dieta sem inclusão da enzima apresentou resultados inferiores ao uso das dietas contendo fitase, resultando em um índice de eficiência produtiva com melhores resultados em dietas contendo 500 e 1500 FTU/Kg de ração da enzima. Houve interação entre o nível de cálcio e fosforo na dieta e adição de fitase para os parâmetros de ganho de peso e resistência óssea que neste trabalho foi representada pela força máxima (N). / This trial was conducted with the objective of evaluating the reduction of calcium and phosphorus available for broilers fed diets containing increased levels of phytase. One thousand and one hundred and fifty-two male chicks Cobb-500 (n = 1152) were submitted to a completely randomized factorial 3 x 4 (three levels of calcium and phosphorus available and four levels of phytase and were distributed among 12 treatments and 8 replicates with 12 broilers each replicate. The experimental treatments were: T1 - diet containing calcium and phosphorus availableas proposed by Rostagno et al. (2011) for different phases; T2 diet containing 90% of calcium and phosphoru available in the diet as proposed by Rostagno et al. (2011) for different phases; T3 - diet containing 80% of calcium and available phosphorus in the diet as proposed by Rostagno et al. (2011) for different phases; T4 - T1 Diet + phytase 500 FTU/Kg diet; T5 - T2 Diet + phytase 500 FTU/Kg diet; T6 - T3 Diet + phytase 500 FTU/Kg diet; T7 - T1 Diet + phytase 1.000 FTU/Kg diet; T8 - T2 Diet + phytase 1.000 FTU/Kg diet; T9 - T3 Diet + phytase 1.000 FTU/Kg diet; T10 - T1 Diet + phytase 1.500 FTU/Kg diet; T11 - the T2 diet + phytase 1.500 FTU/Kg diet; T12 - T3 Diet + phytase 1.500 FTU/Kg diet. The diets were corn and soybean meal - based. The broilers were weighed at 7, 21 and 42 days of age. Performance traits s were evaluated and, at 42 days of age. Carcass yield and commercial cuts were also evaluated. Furthermore, a bone quality study, with the analysis of density and tibial resistance, were performed. The increased levels of phytase in the diets determined a linear increased in average weight gain at 7 and 21 days of age. Likewise, the increased levels of phytase in the diets reduced linearly the feed conversion at 21 days of age. Considering the period from day 1 to day 42 the diets without phytase determined inferior results than the diets with phytase inclusion. The better results were found when the diets have between 500 and 1500 FTU of phytase per kg of concentrate. There were an interaction between the calcium and phosphorus levels with phytase concentration for weight gain e bone resistance. In this work, those parameters were represented by the maximum strength (N).

Objetivou-se elaborar uma revisão sistemática da literatura das exigências de cálcio e fósforo com o uso da enzima fitase em ração para frangos de corte e avaliar altas doses de 6-fitase híbrida em rações, com ajuste na matriz nutricional, sobre o desempenho produtivo, aspectos econômicos, qualidade óssea e características de carcaça de frangos de corte. Para a revisão sistemática adotou-se a metodologia proposta por Lovatto et al. (2007), com a localização de artigos relacionados com o tema, coleta de dados, análise crítica dos artigos, interpretação e representação dos resultados encontrados. Para o desempenho, conduziu-se um experimento com 1200 pintos de um dia, Cobb500®, com peso médio de 47,94 &plusmn; 0,54 g, distribuídos em um delineamento em blocos casualizados com cinco tratamentos, com oito repetições de 30 aves cada. Os tratamentos utilizados foram: 1) Controle positivo de acordo com as exigências da Tabela Brasileira para Aves e Suínos; 2) Controle negativo (CN) com redução na matriz nutricional equivalente a dose de fitase de 750 FTU/kg, mas sem a inclusão da enzima; 3) CN com inclusão da fitase em 750 FTU/kg; 4) CN com inclusão da fitase em 1000 FTU/kg; e 5) CN com inclusão da fitase em 1500 FTU/kg. A redução dos nutrientes no controle negativo foi de 0,184% de fósforo disponível, 84,8 kcal/kg de energia metabolizável, 0,36% de proteína bruta, 0,206% de cálcio, 0,002% de sódio, 0,006% de lisina digestível e 0,019% de metionina+cistina digestível. A enzima utilizada foi Natuphos® E 10.000 FTU/g, nova 6-fitase de origem híbrida. Para o desempenho e o rendimento de carcaça foram observadas diferenças entre os tratamentos (p&lt;0,05), sendo que o controle negativo gerou resultados inferiores em relação aos demais tratamentos, enquanto que, para a análise econômica gerou resultados inferiores para as receitas brutas e superiores para os custos de produção (p&lt;0,05). Para a qualidade óssea, a suplementação de fitase nos níveis de 1000 e 1500 FTU/kg geraram resultados semelhantes aos encontrados para o controle o positivo (p&lt;0,05). Dessa maneira, concluiu-se que a suplementação da 6-fitase híbrida em níveis de 1000 e 1500 FTU/kg, com redução de nutrientes na matriz nutricional, melhora o desempenho, as características de carcaça, os aspectos econômicos e os parâmetros de qualidade óssea, conseguindo alcançar a mesma qualidade óssea do controle positivo, porém com um custo reduzido. / The objective of this study was to systematically review the literature on calcium and phosphorus requirements with the use of phytase enzyme in broiler feed and evaluate the levels of hybrid 6-phytase in diets, with an adjustment in the nutritional matrix, on the productive performance, bone quality, and carcass characteristics of broiler chickens. For the systematic review, the methodology proposed by Lovatto et al. (2007), for the localization of articles related to the theme, data collection, critical analysis of the articles, interpretation and representation of the results found. For broilers from 1 to 21 days, the enzyme phytase Natuphos is the most studied and levels above 500 FTU / kg can be used without compromising the performance of the animals, in addition to significantly improving the cost of. An experiment was carried out with 1200 day-old Cobb500® chickens, with a mean weight of 47.94 &plusmn; 0.54 g, distributed in a randomized block design with five treatments, with eight replicates of 30 birds each. The treatments used were: 1) Positive control according to the requirements of the Brazilian Poultry and Pork Table; 2) Negative control (CN) with reduction in nutritional matrix equivalent to phytase dose of 750 FTU / kg, but without inclusion of the enzyme; 3) CN with phytase inclusion at 750 FTU / kg; 4) CN with phytase inclusion at 1000 FTU / kg; and 5) CN with phytase inclusion at 1500 FTU / kg. The nutrient reduction in the negative control was 0.184% of available phosphorus, 84.8 kcal / kg of metabolizable energy, 0.36% crude protein, 0.206% calcium, 0.002% sodium, 0.006% digestible lysine and 0.019 % digestible methionine + cystine. The enzyme used was Natuphos® E 10,000 FTU / g, a novel 6-phytase of hybrid origin. For carcass performance and yield, differences between treatments (p &lt;0.05) were observed, and the negative control generated lower results in relation to the other treatments, whereas, for the economic analysis, lower results were obtained for gross and production costs (p &lt;0.05). For bone quality, phytase supplementation at 1000 and 1500 FTU / kg levels were found to be similar to the positive control results (p &lt;0.05). Thus, it is concluded that supplementation of hybrid 6-phytase at levels of 1000 and 1500 FTU / kg, with nutrient reduction in the nutritional matrix, improves performance, carcass characteristics, economic aspects and parameters of bone quality, achieving the same quality bone of the positive control, but with a reduced cost.

O sucesso do tratamento de implantes dentários depende da quantidade e qualidade óssea da área de interesse e o uso da Tomografia Computadorizada por Feixe Cônico (TCFC) pode ser correlacionado para a sua estimativa. O objetivo deste estudo foi avaliar e comparar os níveis de escala de cinza dos voxels de imagens obtidas por TCFC de mandíbulas atróficas com o auxílio de programa para diagnóstico e planejamento de implantes e correlacionar a Intensidade Pixel (IP) com a classificação subjetiva do Índice de Qualidade Óssea (IQO). Foram avaliadas imagens tomográficas de 10 mandíbulas atróficas obtidas do banco de dados do LAPI-FOUSP (Laboratório para Análise e Processamento de Imagens) que receberam 8 marcações em regiões normalmente utilizadas para colocação de implantes (4 em região anterior e 4 em região posterior), sobre estas foram posicionados fios ortodônticos para padronização dos cortes tomográficos e simular posições ideais de implantes. Cortes transaxiais das áreas demarcadas foram obtidas para visualização e análise de 4 regiões corticais e 3 regiões trabeculares do tecido ósseo de cada corte, para a seleção de área foi utilizada a ferramenta Região de Interesse (ROI) de cada programa. As imagens foram analisadas por 3 programas de planejamento Romexis (Planmeca,Finlandia), XoranCAT® (Xoran Technologies, EUA) e OsiriX® (Free Software Foundation, 32 bits, EUA). Os dados foram submetidos a análise estatística de Correlação de Spearman em um nível de significância de 5% (p<0,05), análise de correlação intraclasse intra-observador e inter-observador pelo teste Kappa ponderado e o teste qui-quadrado. Os resultados apresentaram que os programas Romexis e OsiriX apresentaram melhor acuidade para a avaliação subjetiva de qualidade óssea, em contrapartida o programa Xoran apresentou inconsistência de dados. Concluiu-se que há correlação entre Intensidade de Pixel e Qualidade óssea de acordo com os resultados encontrados para os programas OsiriX e Romexis / The success of dental implants treatment depends on the bone quantity and quality of the area of interest and the use of Cone Beam Computed Tomography (CBCT) can be correlated to an estimative. The aim of this study was to evaluate and compare the grey scale levels of voxels obtained by CBCT of atrophic mandibles with the aid of software for diagnosis and planning implants and correlates the Pixel Intensity (PI) with the subjective classification of Bone Quality Index (BQI). Tomographic images of 10 atrofic mandibles obtained from the data base of LAPI-FOUSP (Laboratory of analysis and imaging processing) were evaluated, received 8 marks in areas normally used for implant placement (4 in anterior and 4 in posterior region) on these orthodontic wires were positioned for standardization of tomographic images and simulate optimal implant positions. Transaxial slices of the demarcated areas were made for visualization and analysis of four regions of interest for cancellous bone and three regions of interest for cortical bone and for selection of each area a tool called Region of Interest (ROI) was used by each software. The images were analised by three diferent planning software, Romexis (Planmeca, Finland), XoranCAT® (Xoran Technologies, EUA) e OsiriX® (Free Software Foundation, 32 bits, EUA). Data were subjected to statistical analysis of Spearman correlation, intraclass intra-observer and inter-observer analysis correlation and weighted Kappa concordance coefficient with 5% significance level and chi-squared test; The results presented that Romexis and OsiriX software showed better accuracy for subjective assessment of bone quality, on the other hand Xoran software showed data inconsistency. This study concluded that a correlation was found between Pixel Intensity (PI) and Bone Quality (BQ) due to the results of OsiriX and Romexis software.

Bone quality influences bone strength with important consequences for osteoporosis, fracture risk and dental implant success. Whilst imaging that is capable of capturing bone structure in 3D is becoming more common, quantitative clinical measures of bone quality rely on bone quantity, not structure. If bone quality could be more accurately measured, and the influence of bone architecture better understood, strength may be better predicted. This thesis presents methods for making structural comparisons between successive micro-CT images of loaded bone and explores the limitations of these. I present a novel method to detect where damage occurs in loaded rat vertebrae based on multiscale rigid registration and difference measures. Together these methods represent a quantitative approach to image guided failure analysis. Time-lapsed micro-CT images of 14 successively loaded rat vertebrae were acquired and damaged regions found using these. Using a random forest classifier I tested whether the damaged regions could be predicted by several commonly used structural measures (bone area and volume), three-dimensional texture measures (co-occurrence matrices and fractal dimension) and a more novel type of architectural measure (based on the structure tensor). A combination of parameters was able to predict damage regions with specificities in the range 70-90% and sensitivities of 60-70%.Using ovariectomised rats as a model of osteoporosis I have performed a pilot experiment to investigate how changes in bone quality might effect our results. The wider applicability of my methods are demonstrated by applying them to dental cone beam images of healthy and osteoporotic patients.

L’ostéoporose ménopausique par une accélération du remodelage osseux, conduit à une masse osseuse basse et à des altérations de la microarchitecture, augmentant ainsi le risque de fracture. Les bisphosphonates diminuent l’activité du remodelage osseux en inhibant la résorption osseuse qui conduit à un maintien de la densité minérale osseuse et à une diminution du risque fracturaire. Ce traitement étant la plupart du temps chronique, l’étude de ses effets sur les différents niveaux d’organisation de l’os, du cristal à sa macrostructure, est primordiale. A travers deux études portant sur l’ibandronate et l’alendronate, nous avons montré que leur utilisation préservait la minéralisation osseuse tissulaire. Cependant, une utilisation prolongée (6,4 ans) de l’alendronate, nous a permis de mettre en évidence un mécanisme d’action impliquant des modifications de la structure des cristaux avec un effet sur les propriétés mécaniques locales. Si l’efficacité anti fracturaire de l’alendronate est démontrée après dix ans de traitement, nos résultats suggèrent des altérations de la qualité osseuse à une échelle plus locale / Postmenopausal osteoporosis is characterized by an increase in remodelling activity leading to a low bone mass and alterations in microarchitecture, increasing the risk of fracture. Bisphosphonates slowdown remodeling inhibiting bone resorption, thus bone mineral density is preserved with a decrease in the risk of fracture. Such a treatment is often chronic, making the study of their long-term effects on multiscale bone quality (from the crystal to the macrostructure) of clinical relevance. Thank to two different studies on ibandronate and alendronate, we showed that these treatments preserved the mineralization of bone tissue. However, we firstly described that a long-term treatment with alendronate alter the structure of bone mineral crystals with a direct effect on micromechanical properties. Even if, the reduction in the risk of fracture under alendronate has been established after a ten year treatment, our results suggest alterations in bone quality at tissular and sub-tissular levels of organization