Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat Type 2 Diabetes Mellitus (T2DM). Clinical trials show that women taking RSG experience more limb fractures than patients taking other T2DM drugs. The purpose of this study is to understand how RSG (3mg/kg/day and 10mg/kg/day) and the bisphosphonate alendronate (0.7mg/kg/week) alter bone quality in the male, female and female ovariectomized (OVX) Zucker fatty rat model over a 12 week period. Bone quality was evaluated by mechanical testing of cortical and trabecular bone. Microarchitecture, bone mineral density (BMD), cortical bone porosity, bone formation/resorption and mineralization were also measured. Female OVX RSG10mg/kg rats had significantly lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented these negative effects in the OVX RSG model. Evidence of reduced bone formation and excess bone resorption was detected in female RSG-treated rats.

Homing is the process that stem cells move to their own stem cell niches under the influence of chemokines like stromal-derived factor-1&alpha / (SDF-1&alpha / ) upon bone marrow transplantation (BMT). There is a need for increasing homing efficiency after BMT since only 10-15% of the transplanted cells can home to their own niches and a limited amount of donor marrow can be transplanted. In this study, we aimed to develop and characterize bone marrow targeted liposomal SDF-1&alpha / delivery system prepared by extrusion method. Alendronate conjugation was chosen to target the liposomes to bone marrow microenvironment, particularly the endosteal niche. Optimization studies were conducted with the model protein (

No description available.

Osteoporosis is a significant healthcare issue due to the increasing elderly population. Bisphosphonates are used to treat osteoporosis by reducing the rate of resorption, increasing bone mineral density (BMD) and thereby reducing fracture risk. Long-term bisphosphonate treatment, however, has been associated with low-energy fractures. Bone microdamage may provide a partial explanation for one of the mechanisms responsible for these fractures since it has been shown to reduce bone toughness, fracture resistance, and bone strength. The goal of this study was to quantify the changes in bone microdamage parameters with the duration of bisphosphonate treatment. This study selected, stained, and histomorphometrically analyzed 40 iliac crest bone biopsies from controls and female patients with osteoporosis treated with bisphosphonates for varying durations (up to 12 years). All subjects were matched for age and low turnover. The results showed that microcrack density and microcrack surface density were significantly greater in patients who took bisphosphonates for at least 5 years compared to those who took bisphosphonates for less than 5 years or not at all. These results reveal novel, clinically relevant information linking microdamage accumulation to long-term bisphosphonate treatment without influences from age or turnover.

Made available in DSpace on 2015-05-14T12:56:01Z (GMT). No. of bitstreams: 1 ArquivoTotalStela.pdf: 1718832 bytes, checksum: fcb910074921d64170b58b950c91c599 (MD5) Previous issue date: 2013-03-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study aims to evaluate the effect of 0.5% (5mg/ml) and 1% (10mg/ml) alendronate sodium (ALN) associated or not with lyophilized bovine bone (Bio-Oss®) on the repair of calvaria bone defects in rabbits. Two bony defects, 10mm diameter circular, were created in 40 male New Zealand white rabbits. The animals were randomized into five (n = 8) groups: GI = Bio-Oss®; GII = Bio-Oss® + ALN 0.5%; GIII = Bio-Oss® + ALN 1%; GIV = ALN 0. 5%; GV = ALN 1%. The left defect was filled with the corresponding substance of each experimental group and the right defect was filled with autogenous blood clot (control). All cavities were lined and covered with a biological membrane. The animals were euthanized 30 and 60 days after craniotomy. The percentage of new bone formation was assessed by microradiographic analysis of calvaria. The images obtained were analyzed using the public domain program Image J®, to assess quantitatively the percentage of bone repair. The values obtained were analyzed using the software SPSS® Statistics, using descriptive statistics (mean, standard deviation and confidence intervals) and inferential ("t" - Student and ANOVA/Tukey). The intragroup results showed that in GI, GII and GIII the percentage of bone repair was significantly higher in the experimental side compared to their respective controls; and was not statistically difference in GIV and GV groups, between experimental and controls sides. The intergroup results showed the following percentage of repair at 30 days: GI = 61.91% (± 10.61), GII = 80.39 (± 8.68), GIII = 81.60% (± 5.42), GIV = 48.45% (± 6.54), GV = 41.45% (± 8.98) and at 60 days: GI = 83.23% (± 14.43), GII = 98.72% (± 2.54), GIII = 92.66% (± 9.22), GIV = 50.18% ( ± 3.03), GV = 37.46% (± 6.26). It is concluded that the addition of alendronate in concentrations of 0.5 and 1%, to lyophilized bovine bone, accelerate the process of bone repair, being more significant in lower concentration. The use of ALN alone delayed the process of bone repair, but without statistical significance. / A presente pesquisa teve como objetivo avaliar o efeito do alendronato de sódio (ALN), nas concentrações de 0,5 (5mg/ml) e 1% (10mg/ml), associadas ou não ao osso bovino liofolizado (Bio-Oss®), na reparação de defeitos ósseos produzidos em calvária de coelhos. Foram utilizados 40 coelhos machos brancos da raça Nova Zelândia. Na calvária de cada animal, foram confeccionados dois defeitos medindo 10 mm de diâmetro. Os animais foram distribuídos aleatoriamente em cinco grupos (n=8 cada): GI = Bio-Oss®; GII = Bio-Oss®+ALN 0,5%; GIII = Bio-Oss®+ALN 1%; GIV = ALN 0,5%; GV = ALN 1%. A cavidade esquerda foi preenchida pela substância correspondente a cada grupo experimental e a cavidade direita preenchida por coágulo sanguíneo autógeno (controle de cada grupo). Todas as cavidades foram forradas e cobertas por membrana biológica. Os animais foram eutanasiados aos 30 e 60 dias após a craniotomia. O percentual de neoformação óssea foi avaliado por meio de análise radiomicrográfica da calvária. As imagens obtidas por radiomicrografia foram analisadas através do programa de domínio público Image J®, para avaliar quantitativamente o percentual de reparo ósseo. Os valores obtidos pelo Image J® foram submetidos à análise com auxílio do software SPSS® Statistics, por meio de estatística descritiva (média, desvio-padrão e intervalos de confiança) e inferencial (teste t Student e ANOVA/ Tukey). Na comparação intragrupos, os resultados demonstraram que nos grupos GI, GII e GIII o percentual de reparo foi significantemente mais elevado no lado experimental em relação aos respectivos controles; nos grupos GIV e GV não foram observadas diferenças estatisticamente significativas no percentual de reparo entre os lados experimental e controle. Na comparação intergrupos, os resultados mostraram os seguintes percentuais de reparo aos 30 dias: GI = 61,91% (± 10,61), GII = 80,39 (± 8,68), GIII = 81,60% (± 5,42), GIV = 48,45% (±± 6,54), GV = 41,45% (± 8,98). Aos 60 dias: GI = 83,23% (± 14,43), GII = 98,72% (± 2,54), GIII = 92,66% (± 9,22), GIV = 50,18% (± 3,03), GV = 37,46% (± 6,26). Conclui-se que a adição do ALN, nas concentrações de 0,5 e 1%, ao osso bovino liofilizado aplicado topicamente nos defeitos ósseos acelerou o processo de reparo ósseo, sendo mais significativo na menor concentração. O uso do ALN isoladamente retardou o processo de reparo ósseo, mas sem significância estatística.

O objetivo do presente estudo foi avaliar ossos maxilares e lesões periapicais induzidas em ratas ovariectomizadas submetidas ou não ao tratamento com bisfosfonato (Alendronato - ALD) ou com inibidor da catepsina K (Odanacatib - ODN). Foram utilizadas 45 ratas, divididas em 6 grupos: I sham (cirurgia de ovariectomia fictícia); II sham e lesão periapical (LP); III - ovariectomia (OVX) sem LP; IV OVX e LP; V OVX, LP e ALD; e Grupo VI - OVX, LP e ODN. Um dia após a realização da OVX ou da cirurgia fictícia, os animais dos grupos V e VI começaram a receber ALD ou ODN, via gavagem. Decorridas 9 semanas da realização da OVX, os primeiros molares dos grupos II, IV, V e VI foram submetidos à indução de LP por 3 semanas. Decorrido este período, foi realizada colheita microbiológica dos canais radiculares para a quantificação de micro-organismos e os animais foram submetidos à eutanásia. Fêmures foram analisados por meio de densitômetro, para registro da densidade mineral óssea (BMD). As maxilas foram analisadas por meio de microtomografia computadorizada (micro-CT) para avaliação da microarquitetura e BMD do osso interradicular e as mandíbulas para avaliação do volume das LP. Os primeiros molares inferiores foram submetidos ao processamento histotécnico, sendo os cortes corados com hematoxilina e eosina (HE) e analisados em microscopia convencional. Paralelamente, foi realizada a análise morfométrica da área das lesões periapicais, em microscopia de fluorescência e histoenzimologia para a atividade da TRAP. Os primeiros molares superiores foram submetidos à detecção da expressão gênica de citocinas, marcadores da osteoclastogênese e de metaloproteinases da matriz. Os resultados obtidos foram submetidos à análise estatística apropriada, com nível de significância de 5%. A OVX afetou a BMD do fêmur e da maxila e a microarquitetura apenas do fêmur. O ALD recuperou a BMD dos ossos avaliados. A OVX não foi capaz de influenciar nos níveis de contaminação microbiana do canal radicular. As LP dos animais do grupo IV apresentaram expressão aumentada de RANK, RANKL, IL-1β, IL-6, TNF-α, MMP-8 e 13, enquanto o tratamento com ALD (grupo V) foi capaz de reduzir a expressão de IL-6 e MMP-8, ao mesmo nível que nas LP do grupo II. Além disso, as LP do grupo IV foram maiores (área e volume), em comparação às dos grupos II e V. O ODN, na dose e frequência de administração aplicada, não foi capaz de promover alterações significantes. A OVX e os tratamentos antirreabsortivos não influenciaram no número de osteoclastos ao redor da LP. Assim, concluiu-se que a condição hipoestrogênica induzida pela OVX foi capaz de diminuir a BMD do fêmur e da maxila e alterou a microarquitetura do fêmur. Apenas o ALD foi capaz de recuperar o fenótipo da BMD, ou seja, retorno aos níveis observados nos animais saudáveis. Ainda, a OVX agravou o processo de reabsorção, a inflamação e a expressão de MMPs, provocando lesões periapicais maiores. O ALD e o ODN proporcionaram uma melhora da resposta periapical. Entretanto, apenas o tratamento com ALD recuperou o fenótipo, fazendo com que as lesões periapicais fossem similares às lesões dos animais saudáveis. / The aim of this study was to evaluate maxillary bones and apical periodontitis induced in ovariectomized rats treated or not with bisphosphonate (Alendronate - ALD) or cathepsin K inhibitor (Odanacatib - ODN). Forty-five female rats were divided into 6 groups: I sham surgery; II - sham and apical periodontitis (AP); III - ovariectomy (OVX) without AP; IV - OVX and AP; V - OVX, AP and ALD; and Group VI - OVX, AP and ODN. One day after OVX or sham surgery, the animals in groups V and VI started receiving ALD or ODN, by gavage. After 9 weeks, the first molars of the rats in groups II, IV, V and VI were subjected to induction of AP for 3 weeks. Microbiological root canal sampling was collected for quantification of microorganisms and the animals were euthanized. Bone mineral density (BMD) of the femurs was analyzed by bone densitometry. The maxillas were analyzed by microcomputed tomography (micro-CT) to determine the microarchitecture and BMD of the interradicular bone while the mandibles were analyzed to determined AP volume. The mandibular first molars were subjected to histotechnical processing and hematoxylin and eosin-stained histological sections were examined with conventional microscopy. In addition, a morphometric analysis of AP area was performed using fluorescence microscopy and tartrate-resistant acid phosphatase (TRAP) histoenzymology. The maxillary first molars were used to evaluate the gene expression of cytokines, osteoclastogenesis markers and matrix metalloproteinases (MMP) using RT-PCR. The results were subjected to appropriate statistical analysis with 5% significance level. OVX affected femoral and maxillary BMD and femoral microarchitecture. ALD recovered the BMD of both types of bones. OVX was not able to influence the microbial levels of the root canal. In group IV, AP showed increased expression of RANK, RANKL, IL-1β, IL-6, TNF-α, MMP-8 and MMP-13, while ALD treatment (group V) reduced IL-6 and MMP-8 expression to the same level as the AP in group II. In group IV, AP area and volume were larger than in groups II and V. ODN, in the dosage and frequency of administration applied, was not able to promote significant changes. OVX and antiresorptive treatments did not influence the number of osteoclasts around the AP region. In conclusion, the hypoestrogenic condition induced by OVX was able to decrease the BMD of femur and maxilla and only the microarchitecture of the femur. ALD was able to recover the BMD phenotype, i.e., return to the levels observed in healthy animals. Furthermore, OVX exacerbated resorption, inflammation and MMP expression, inducing larger lesions. Treatment with ALD and ODN resulted in an improvement of the periapical response. However, only ALD recovered the phenotype, with AP similar to that of healthy animals.

Made available in DSpace on 2014-06-11T19:31:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-07Bitstream added on 2014-06-13T19:01:32Z : No. of bitstreams: 1 castilho_lr_dr_araca.pdf: 543044 bytes, checksum: c8c840ddb273d1f9081ffe2d929ea3fa (MD5) / O uso de substâncias que inibem o processo reabsortivo pode ser uma alternativa para o aumento do sucesso nos casos de reimplante tardio. O alendronato sódico é um conhecido inibidor da reabsorção, sendo que sua utilização em forma de pasta, como curativo intracanal, poderia aumentar os índices de sucesso em dentes susceptíveis à reabsorção. Frente a isso, este trabalho teve como objetivo avaliar comparativamente o efeito das pastas de alendronato sódico e hidróxido de cálcio como medicação intracanal em dentes de ratos reimplantados tardiamente. Para isso, foram utilizados 24 incisivos superiores direitos de ratos. Os dentes foram extraídos e permaneceram a seco por 30 minutos, após isso tiveram a superfície radicular tratada com hipoclorito de sódio a 1% e fluoreto de sódio a 2%. Na sequência, os dentes foram divididos em 2 grupos: no grupo I, os canais radiculares foram limpos e preenchidos com a pasta experimental a base de alendronato sódico. No grupo II, usou-se a pasta de hidróxido de cálcio, após os procedimentos citados anteriormente. Em seguida, os dentes foram reimplantados em seus respectivos alvéolos. Passados 15 e 60 dias do reimplante dentário, os animais sofreram eutanásia e as peças obtidas processadas em laboratório para análise microscópica e morfométrica. Os resultados demonstraram que em ambos os grupos a ocorrência da anquilose foi baixa, assim como a reabsorção inflamatória e por substituição. A presença de cemento sobre a superfície radicular foi alta e constante. No grupo I, o tecido conjuntivo formado no espaço do ligamento periodontal mostrou-se disposto de forma paralela, sendo que em alguns espécimes, o tecido estava inflamado e com presença de placa bacteriana, sugerindo a formação de bolsa periodontal. No grupo II, houve a formação de tecido conjuntivo paralelo na maioria... / The search for substances that may increase the success in cases of replantation is a priority. The use of substances that inhibit root resorption may be an alternative for the control of root resorption, especially in cases of delayed replantation. Sodium Alendronato is a unhibitor of bone resorption and it is used as dressing the intracanal in form of paste. This substance increased success rates in case of tooth replantation. So the objective of this study was to evaluated the effect of an experimental paste with alendronate basis used as intracanal dressing in late reimplanted rat teeth. There were used 24 right rats incisors. The teeth were avulsed and kept dry for 30 minutes, after which root surfaces were treated with sodium hypochlorite 1% and sodium fluoride 2%. The roots canal were instrumented and filled with Aledronate sodium paste (Grou I) and calcium hydroxide paste (Group II). In group II, we used the calcium hydroxide paste. Teeth were replanted in their respective sockets. After 15 and 60 days after tooth replantation, the animals were killed and the specimens were processed for morphometric and microscopic analysis The results showed that in group I there were less ankylosis, inflammatory reporotion and replacement comparing to group II. The connective tissue formed in the periodontal ligament space was found to be inflamed by the presence of plaque and periodontal pocket formations. The connective tissue arranged in parallel to the root surface was constant in group I. However this tissue in group II had a significant increase over time. The cement was absent in small proportions and similarly in all experimental groups. The number of gaps of inflammatory resorption was low in both groups. The same happened with the shortcomings of replacement resorption Thus, these findings contraindicate the use of this folder of alendronate for the treatment of intracanal late reimplanted teeth

Made available in DSpace on 2014-06-11T19:33:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-17Bitstream added on 2014-06-13T19:22:56Z : No. of bitstreams: 1 giro_g_dr_arafo.pdf: 2606543 bytes, checksum: ec3040a973d9fcf21be5856e46e14736 (MD5) / O presente projeto teve como objetivo avaliar a influência da deficiência de estrógeno, e as implicações dos tratamentos com alendronato e estrógeno, sobre o tecido ósseo ao redor de implantes. Para isso foram realizados dois estudos distintos, visando elucidar as questões em torno desse tema. No primeiro estudo, foram utilizadas ratas Wistar, com idade aproximada de 60 dias, submetidas à colocação de um implante na metáfise tibial com o objetivo de avaliar a influência da deficiência estrogênica e dos tratamentos com alendronato e estrógeno sobre o tecido ósseo em implantes que já se encontravam osseointegrados. Os resultados mostraram efeitos deletérios da referida deficiência, com diminuição da força de torque necessária para remoção dos implantes, menor quantidade de osso em contato com a superfície e área de osso entre as roscas, aumento nos marcadores de remodelação óssea e menor taxa de aposição mineral no período avaliado. Por outro lado, os animais que receberam a administração do alendronato apresentaram os melhores resultados para todas as análises realizadas, apesar do tecido ósseo mostrar-se mais compacto e sem sinais de remodelação. Concluiu-se que a deficiência estrogênica decorrente da ovariectomia (OVX) acarretou alterações sistêmicas, como perda de massa óssea, e alterou as características do tecido ósseo ao redor dos implantes. Esse quadro pôde ser revertido com os tratamentos instituídos, tendo o alendronato apresentado os melhores resultados. O segundo estudo visou avaliar os efeitos da deficiência de estrógeno e de diferentes dosagens de alendronato, sobre implantes instalados na maxila de ratas e, portanto, sob influência da carga mastigatória. Nesse estudo foram avaliadas também as implicações da instalação de implantes em animais que estavam sob terapia... / This study aimed the evaluation of the influence of bone mass loss and its therapies on bone tissue around osseointegrated implants. For that reason two major projects were conducted. First of all, two implants were placed in 66 female rats tibiae. The animals were assigned to 5 groups: control (CTL), sham, ovariectomy (OVX), oestrogen (EST) and alendronate (ALE). While CTL was sacrificed 60 days after implant placement, other groups were subjected to ovariectomy or sham surgery according to group and euthanized after 90 days. Blood and urine samples were collected at sacrifice day for osteocalcin and deoxypyridinoline quantification. Densitometry of femur and lumbar vertebrae were performed in order to evaluate rats’ skeletal impairment. One implant was subjected to the removal torque test, while the remaining one was referred to non-decalcified sections and analysed by fluorescent and light microscopy for analyses of mineral apposition rate (MAR), eroded and osteoclastic surfaces, bone to implant contact (BIC), and bone area fraction occupancy (BAFO). The results of this study showed that OVX presented significantly lower values for all parameters analysed compared to other groups. ALE increased bone mineral density and the removal torque of the implants, but also reduced osteocalcin and deoxypyridinoline concentrations, MAR, osteoclastic and eroded surfaces, and no difference was in BIC and BAFO relative to SHAM. EST and CTL showed similar results to SHAM for measurements. The results lead the authors to conclude that oestrogen deficiency exerted a negative influence on bone tissue around implants, while oestrogen replacement therapy and alendronate were effective against its effects. Although alendronate therapy maintained the amount of bone tissue around implants, studies evaluating bone turnover kinetics ... (Complete abstract, click electronic access below)

Made available in DSpace on 2014-06-11T19:28:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-03-24Bitstream added on 2014-06-13T20:36:53Z : No. of bitstreams: 1 giro_g_me_arafo.pdf: 376478 bytes, checksum: 41b9f6bee6825f87f572627898751b2f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / O presente estudo teve como objetivo avaliar a influência da deficiência de estrógeno promovida pela ovariectomia (OVX) sobre o tecido ósseo ao redor de implantes com osseointegração estabelecida. Foram utilizadas ratas Wistar, com idade aproximada de 60 dias e peso variando entre 180g a 220g, submetidas à colocação de um implante na metáfise tibial. Os tratamentos utilizados foram eficientes na prevenção da perda óssea. Os animais que receberam a administração do alendronato apresentaram os melhores resultados para todas as análises realizadas. A deficiência de estrógeno decorrente da OVX acarretou prejuízos para a BMD, densidade radiográfica da região de osso medular e torque de remoção dos implantes. Esse quadro pôde ser revertido com a utilização dos tratamentos instituídos, com o alendronato apresentando os melhores resultados. / The aim of the present study was to evaluate the influence of estrogen deficiency due to ovariectomy (OVX) on the bone around osseointegrated titanium implants. Wistar female rats - approximately 60 days old, weighting from 180 to 220 g - were used. Digital radiographs were taken and the implants were submitted to the removal toque. The results showed a negative effect of the OVX on the BMD at the femur and lumbar regions, on the radiographic bone density at the cancellous bone and on the biomechanical characteristics of the bone tissue around the implants. The treatments were efficient preventing bone loss. The animals that received alendronate therapy showed the best results for all the analyzed variables. we can conclude that the estrogen deficiency due to OVX had a negative influence on the BMD, on the radiographic bone density at the cancellous bone and on the removal torque of the implants; however, such negative influence can be reversed with the adopted therapies, among which the alendronate seemed to be the best method for prevention and treatment of bone loss due to OVX.