Current treatment for spinal metastasis involves a multimodal approach, including bisphosphonates and radiation therapy. Yet, tumour response varies considerably, thus novel treatments or combination therapies are needed to treat these metastases while preserving stability and integrity of the spinal column. Photodynamic therapy (PDT) has been shown to be successful in destroying vertebral osteolytic tumours and enhancing vertebral structure, particularly in combination with bisphosphonates. This thesis aims to evaluate the longer-term effects of PDT alone and in combination with bisphosphonate or radiation therapy on healthy vertebrae, and the short-term effects of PDT combined with radiation therapy on healthy and metastatically-involved vertebrae. The benefits of PDT on vertebral structure, both at short-term and longer-term time-points, were greatest in combination with previous bisphosphonate therapy. Similar effects, to a lesser magnitude, were seen with PDT in combination with radiation therapy. This work supports future translation of PDT for the treatment of spinal metastases.

Current treatment for spinal metastasis involves a multimodal approach, including bisphosphonates and radiation therapy. Yet, tumour response varies considerably, thus novel treatments or combination therapies are needed to treat these metastases while preserving stability and integrity of the spinal column. Photodynamic therapy (PDT) has been shown to be successful in destroying vertebral osteolytic tumours and enhancing vertebral structure, particularly in combination with bisphosphonates. This thesis aims to evaluate the longer-term effects of PDT alone and in combination with bisphosphonate or radiation therapy on healthy vertebrae, and the short-term effects of PDT combined with radiation therapy on healthy and metastatically-involved vertebrae. The benefits of PDT on vertebral structure, both at short-term and longer-term time-points, were greatest in combination with previous bisphosphonate therapy. Similar effects, to a lesser magnitude, were seen with PDT in combination with radiation therapy. This work supports future translation of PDT for the treatment of spinal metastases.

With the studies performed in this theses the local drug delivery technique FibMat developed by the biotech company AddBIO, was shown to be applicable to other plasma proteins and drugs than the fibrinogen-bisphosphonate combination that is today being commercialized. Hence the potential for a broader field of application was demonstrated. The application targeted today is as a surface modification giving improved strength to bone around screws used in bone implants. The effect of changing protein and manufacturing conditions was studied with null ellipsometry. It was demonstrated that with changes in incubation temperature, pH and salinity the fibrinogen could be successfully exchanged for the plasma proteins human serum albumin and immunoglobulin G. With liquid scintillation counting it was shown that the developed protein multilayers were able to absorb and release the bone strengthening drug alendronic acid in levels comparable to that of the fibrinogen based ditto. Disk susceptibility tests with the bacteria S. Aureus showed a potential for antibacterial functionalization with gentamicin. The release was, in the case of the fibrinogen multilayer, detectable up to 48 hours. Similar test revealed an inability of silver nanoparticle incorporated protein multilayers to achieve inhibitory levels.

No description available.

Bone’s ability to resist fracture is often ignored until a low-energy fracture occurs. Patients with Chronic Kidney Disease (CKD) or osteoporosis are at an increased risk of low-energy fracture. Generally, fracture risk is evaluated by using a bone mineral density (BMD) test. BMD values; however, do not fully predict bone’s ability to resist fracture. This suggests that other parameters may be involved. Bone quality is the term used to describe these parameters, which are categorized into three groups: structural, material, and microdamage. The aim of this dissertation research was to examine whether bone quality was altered in patients who: 1) had abnormal bone turnover (high or low) due to CKD, 2) suffered a low-energy fracture despite normal BMD, or 3) had osteoporosis and were treated with bisphosphonates. These studies used iliac crest bone specimens from Caucasian females aged 21 to 87 years. Bone’s material parameters were measured by Fourier transform infrared spectroscopy. The key finding from the turnover study was that high and low turnover was associated with altered bone quality. Specifically, bone with high turnover had a lower mineral-to-matrix ratio compared to normal and low turnover (p<0.05), while low turnover had a lower cancellous bone volume and trabecular thickness compared to normal or high turnover (p<0.05). The key finding from the fracture study was that patients with normal BMD and low-energy fractures had altered bone quality (greater collagen crosslinking ratio) compared to patients who had low-BMD with low-energy fractures and healthy subjects (controls) (p<0.05). Lastly, the key findings from the bisphosphonate studies were that osteoporosis patients treated with these drugs had altered bone quality (specifically, greater (p<0.05) mineral-to-matrix ratio) compared to untreated turnover-matched osteoporotic patients, and that were several positive linear correlations with the nanoindentation derived Young’s modulus and hardness of cortical and trabecular bone and the duration of bisphosphonate treatment (p<0.05). The findings presented provide further evidence that bone quantity is not the sole factor in determining bone’s ability to resist fractures and that bone quality is an essential factor.

Background: Using a nude rat model of site-specific metastatic bone disease (MBD), we developed a semiquantitative histological score for rapid assessment of lytic lesions in bone. This provides additional information to conventional histological measurement by clarifying the extent and location of metastatic infiltration and the tumor growth pattern. The score can also be used to assess the action of bisphosphonates on bone metastases. Materials and Methods: Male nude rats (n = 12 per group) were inoculated with the human breast cancer cell line MDA-MB-231 via the femoral artery. Following appearance of radiographically visible osteolytic lesions on day 18, the animals received phosphate-buffered saline (PBS; controls) or ibandronate (IBN, 10 µg P/kg) daily until day 30. Whole body radiographs were obtained on days 18 and 30, and osteolytic areas (OA) were determined by radiographic computer-based analysis (CBA). On day 30, MBD was assessed in both tibias using conventional histological CBA and the new scoring system. Results: Metastatic tumor area correlated with the total sum of the new score in both PBS- (r = 0.762) and IBN-treated animals (r = 0.951; p < 0.001). OA correlated well with the total sum in both groups (r = 0.845 and 0.854, respectively; p < 0.001). Conclusion: Significant reduction of bone marrow and cortical infiltration of tumor cells with IBN suggested local control of metastases. / Hintergrund: Mit Hilfe eines etablierten Tiermodells zur Erzeugung lokalisationsspezifischer Knochenmetastasen in der Nacktratte wurde ein semiquantitatives histologisches Graduierungssystem zur schnellen Bewertung osteolytischer Knochenmetastasen entwickelt. Das Graduierungssystem liefert hinsichtlich der Metastasenlokalisation, deren Ausmaß und Infiltrationsmuster wertvolle Zusatzinformationen zu den konventionellen histologischen Untersuchungsmethoden. Damit kann beispielsweise auch die pharmakologische Wirkung von Bisphosphonaten auf die Knochenmetastasierung beurteilt werden. Material und Methoden: Männlichen Nacktratten (n = 12 pro Gruppe) wurden Zellen der humanen Brustkrebszellinie MDA-MB-231 in die Oberschenkelarterie inokuliert. Ab dem Auftreten radiologisch erkennbarer Osteolysen 18 Tage nach Inokulation erhielten die Tiere bis zum Studienende (Tag 30) täglich entweder eine subkutane Applikation einer Phosphat-Puffer-Lösung (Kontrollgruppe) oder Ibandronat (IBN, 10 µg P/kg; Behandlungsgruppe). Konventionelle Röntgenaufnahmen wurden an den Tagen 18 und 30 nach Tumorinokulation angefertigt und die Osteolysenflächen mittels Computerauswertung bestimmt. Nach Studienende wurde der Metastasenbefall in beiden Tibiae sowohl konventionell histologisch als auch mittels des neuen Graduierungssystems ausgewertet. Ergebnisse: Die Metastasenfläche korrelierte mit der kummulativen Punktsumme des Graduierungssystems sowohl in der Kontrollgruppe (r = 0,762; p < 0,001) als auch in der Ibandronat- Gruppe (r = 0,951; p < 0,001). Ebenso war die Osteolysenfläche eng mit der Punktesumme in beiden Gruppen korreliert (r = 0,845 und 0,854; p < 0,001). Schlussfolgerung: Die signifikante Reduktion von Knochenmark- und Kortikalisbefall durch IBN deuten auf eine gute lokale Kontrolle des Metastasenwachstums hin. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Investigation of activated remodelling in the healing of experimental stress fractures and the influence of anti-inflammatory treatments Lisa Jane Kidd Abstract Targeted and focal remodelling are important processes in bone homeostasis and pathology. However, the factors that initiate and direct remodelling to repair microcracks, or respond to excess loading are still poorly understood. The rat ulna-loading (RUL) model has been widely used to examine modelling and remodelling responses to axial cyclic loading. However the model has not yet been fully characterised. Stress fractures are common amongst athletes, dancers and military recruits, but there is almost no information available on the mechanism of healing of these fractures. Although cyclooxygenase-2 (COX-2) is a key mediator of bone resorption and bone formation, very little information is available on the effect of non-steroidal antiinflammatories (NSAIDs) on stress fracture healing. Remodelling may play a role in the pathogenesis of stress fractures, and there is growing interest in the potential use of bisphosphonates to prevent them. Nonetheless, the effect of bisphosphonates on stress fracture healing is not known. PMX53 is a C5a receptor antagonist developed as a novel anti-inflammatory agent. It is effective against inflammatory arthritis, but has not been tested in any fracture models. The aims of this study were to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by RUL, and to use this model to determine the effects of selective and non-selective NSAIDs, a bisphosphonate and PMX53 on stress fracture healing. To characterise the RUL model, fatigue fractures were created by loading ulnae until displacement was observed to increase by between 4% and 50%. Ulnae were bulk-stained in basic fuchsin and processed for undecalcified histology. For all remaining experiments, loading was stopped when the displacement had increased by 10%. For detailed histology and histomorphometry, ulnae were decalcified, paraffin embedded and stained with toluidine blue, saffranin-O or for tartrate resistant acid phosphatase (TRAP). Ulnae were examined at 1, 2, 4, 6, 8, and 10 weeks after loading. The effects of DFU (a selective COX-2 inhibitor, 2 mg/kg po), ibuprofen (a non-selective NSAID, 30 mg/kg po) and PMX53 (10 mg/kg po) were examined at 2, 4 and 6 weeks after loading. Effects of risedronate (a bisphosphonate) were examined at a high (1.0 mg/kg po) and low dose (0.1 mg/kg po) at 2, 6 and 10 weeks after loading. RUL did not create isolated intracortical microcracks, but curvilinear fatigue fractures that occurred at a standard position in the medial cortex of the distal ulna diaphysis. These stress fractures induced rapid periosteal woven bone formation and direct intracortical remodelling along the fracture line that originated at the periosteum and progressed towards the medullary cavity. Basic multicellular units (BMUs) could be followed through serial sections extending along the fracture line towards the centre of the bone. Quantitative, real-time PCR was performed at 4 hours, 24 hours, 4 days, 7 days and 14 days after fatigue fracture. Following each period, bones were dissected and mRNA was extracted using standard protocols. Gene expression was compared between loaded and unloaded ulnae and to an unloaded control group. Four hours after loading, there was a marked, 220-fold increase (P<0.0001) in expression of Interleukin-6 (IL-6). There were also prominent peak increases in mRNA expression for Osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) (all P<0.0001). At 24 hours there was a peak increase in mRNA expression for IL-11 (73-fold increase, P<0.0001). At 4 days there was a significant increase in mRNA expression for Bcl-2, COX-1, bone morphogenic protein (BMP)-2, insulin-like growth factor (IGF)-1, osteopontin (OPN), and stromal cell derived factor SDF-1. At 7 days there was a significant increase in mRNA expression of Receptor activator of nuclear factor kappa β ligand (RANKL) and OPN. The dramatic, early up-regulation of IL-6 and IL-11 suggests they play a central role in initiating signalling events for stress fracture healing. Treatment with PMX53 did not affect any measures of woven bone formation or stress fracture remodelling. There were no treatment effects of Ibuprofen or DFU on the area of woven bone. DFU treatment resulted in a significant reduction in the area of porosity (resorption) and BMU area along the fracture line at 2 weeks after fracture. Ibuprofen treatment resulted in a significant reduction in length and area of BMUs and new bone formation along the fracture line at 6 weeks (p < 0.05). This is the first report to demonstrate a negative effect on stress fracture healing of both a selective COX-2 inhibitor and a non-selective NSAID. These data confirm the importance of cyclooxygenase in bone resorption and formation during remodelling. Bisphosphonates are potent inhibitors of osteoclastic bone resorption Two, 6 and 10 weeks after loading, measures of resorption and new bone formation were significantly reduced along the fracture line by high dose risedronate treatment, but not by the low dose. Only the porosity along the fracture line 2 weeks after loading was significantly reduced by the low dose risedronate. The low dose more closely resembles the clinical dose used to treat patients. Woven bone formation and consolidation were not affected by the low or high doses of risedronate. In conclusion, fatigue fractures in the rat ulna are highly reproducible, induce exuberant periosteal woven bone formation, and heal by direct remodelling along the fracture line. Remodelling is associated with gene expression for molecules typically associated with bone resorption and formation, angiogenesis and cell signalling. Remodelling of the stress fracture line was adversely affected by treatment with selective and non-selective COX inhibitors, by high dose treatment with risedronate, but not by PMX53, a C5a antagonist.

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-1&beta;, IL-6, TNF-&alpha;, 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-1&beta;, IL-6, TNF-&alpha;, 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 2014-06-11T19:33:00Z (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)

Orientador: Silvana Regina Perez Orrico / Banca: Carlos Rossa Junior / Banca: Luis Carlos Spolidorio / Banca: Márcia Pinto Alves Mayer / Banca: Marcelo de Faveri / Resumo: 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... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: 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) / Doutor