Uma das complicações mais importantes relacionadas com o tratamento de implante dentário é a peri-implantite. Devido a limitação pela sobreposição de estruturas da técnica periapical, nos casos da perda óssea peri-implantar nas faces vestibulares e linguais ou palatais necessita-se de um exame capaz de prover imagens em 3 dimensões para o correto diagnóstico, sendo as imagens de tomografia computadorizada por feixe cônico (TCFC) as mais indicadas. O objetivo deste estudo foi avaliar a acurácia, especificidade, sensibilidade, concordância inter e intraobservadores e determinar a influência dos artefatos na detecção dos defeitos ósseos peri-implantares simulados em mandíbulas humanas edêndulas secas. Foram utilizados dois aparelhos de TCFC com diferentes protocolos de aquisição: i-CAT Gendex CB-500(120kVp, 5mA) e ORTHOPANTOMOGRAPH OP300(90kVp, 6.3mA). Foram instalados 24 implantes dentários cilíndricos e executados dezesseis defeitos somente nas faces vestibulares, com os comprimentos que variaram de 0,5mm a 15mm. Somente cortes sagitais foram utilizados para avaliação qualitativa e quantitativa dos defeitos foi realizada por meio de Image J. Os resultados do teste de concordância intra e inter-observadores tanto nas avaliações qualitativas e quantitativas foram predominantemente fracos. Os valores de Área Sob a Curva (ASC) variaram de 0.51 a 0.72 no i-CAT Gendex CB-500; e no ORTHOPANTOMOGRAPH OP300 variaram de 0.54 a 0.75, demonstrando desempenho diagnóstico ligeiramente superior. Nas imagens obtidas em aparelho com 120kVp (i-CAT Gendex CB-500) foram observados maior contraste em relação ao aparelho 90kVp (ORTHOPANTOMOGRAPH® OP300); em aparelho com o menor kVp (OP300) formaram mais artefatos e estes, degradaram a qualidade das imagens e influenciaram o desempenho diagnóstico das TCFCs na detecção e nas mensurações de perda óssea peri-implantar. Os protocolos de aquisições diferentes podem influenciar no aumento ou redução da formação dos artefatos. / One of the most important complications related to dental implant treatment is periimplantitis. Due to the structures overlapping inherited to periapical technique, in cases of buccal and lingual or palatal bone loss in peri-implantitis, the 3 dimensions observation exam like cone beam computed tomography(CBCT) is most indicated. The objective of this study was to evaluate the accuracy, specificity, sensitivity, interand intra-observer agreement and to determine the influence of the artifacts in the detection of the peri-implant bone defects simulated in human dry mandibles. The two CBCT devices with different acquisition protocols were used in this study: i-CAT Gendex CB-500 (120kVp, 5mA) and ORTHOPANTOMOGRAPH OP300 (90kVp, 6.3mA). Twenty-four cylindrical dental implants were placed and 16 defects were prepared only on buccal faces, the defect lengths ranged from 0.5mm to 15mm. For qualitative and quantitative assessment, only sagittal slices were evaluated by the observers, using Image J software. The results of intra and inter-observer agreement tests in both assessments were generally poor. The AUC values ranged from 0.51 to 0.72 on the i-CAT Gendex CB-500; and in the ORTHOPANTOMOGRAPH OP300 ranged from 0.54 to 0.75, showing slightly higher diagnostic performance. Higher contrast was observed in the 120 kVp device\'s images (i-CAT Gendex CB-500) when compared with the 90 kVp device\'s image (ORTHOPANTOMOGRAPH® OP300). The low kVp device (OP300), formed more artifacts which degraded the image quality and influenced the CBCT diagnostic performance in the detection and measurement of peri-implant bone loss. Different CBCT acquisition protocols may influence increasing or reducing artefact formation.

Made available in DSpace on 2014-12-17T15:43:54Z (GMT). No. of bitstreams: 1 KarynaMM_DISSERT.pdf: 1613458 bytes, checksum: 37ceb3c8bc9380fd82bea372ee1cedb7 (MD5) Previous issue date: 2014-02-20 / It has been shown that the development of peri-implant mucositis is associated with biofilm accumulation. It is believed that the therapeutic approaches used in periodontal disease may have a positive effect in the cases of peri-implant disease. The aim of this study was to evaluate the effectiveness of non-surgical treatment of peri-implant mucositis, with or without the use of chlorhexidine 0,12% in subjects rehabilitated with osseointegrated implants. Thus, patients were randomly divided into test group (chlorhexidine surgical therapy) and control (non-surgical treatment). This therapy consisted of an adaptation of the (Full Mouth scalling and Root Planing) nonoperative protocol FMSRP, but without the use of ultrasound. The visible plaque index (VPI), gingival bleeding index (GBI), probing depth (PD), bleeding on probing (BOP) and keratinized mucosa clinical parameters were evaluated at baseline and at different times after treatment. The data were not normally distributed and the implant was considered the sampling unit. Data were analyzed using Fri edman and Wilcoxon chi-square (&#61537;=5%), tests using the Statistical Package for Social Sciences 17.0 (SPSS). Thus, 119 implants were evaluated, 61 in the test group and 58 in the control group. The results showed statistically significant differences for the variables: average BTI implants in both groups (p<0,001), mean ISG implants both in the test group (p<0,001), and control (p= 0,006) of implants; PS for the test group (p< 0,001) and control (p = 0,015) and SS (p<0,001) in the two treatment groups. However, there was no statistically significant difference when the groups were compared. The PS and SS variables showed no statistically significant difference in any of independent interest to the study (age, sex, smoking, treatment group, keratinized mucosa at different times, peri-implant biotype, average VPI implants and GBI). Thus, it can be concluded that both the mechanical treatment isolated as its association with chlorhexidine mouthwash 0.12% can be used for the treatment of peri-implant mucositis. Moreover, the condition of oral h ygiene has improved between baseline and six months and the depth and bleeding on probing decreased after three and six months / Tem sido demonstrado que o desenvolvimento da mucosite peri-implantar est? associado ao ac?mulo de biofilme dent?rio. Acredita-se que as abordagens terap?uticas utilizadas nas doen?as periodontais podem apresentar efeito positivo nos casos de doen?as peri-implantares. O objetivo desse estudo foi avaliar a efic?cia do tratamento n?o cir?rgico da mucosite peri-implantar em 119 implantes, sendo 61 no grupo teste (digluconato de clorexidina a 0,12%) e 58 no grupo controle (placebo), em indiv?duos reabilitados com implantes. Desta forma, os pacientes foram divididos aleatoriamente em grupo teste (terapia n?o cir?rgica + clorexidina) e controle (terapia n?o cir?rgica). Esta terapia consistiu de uma adapta??o do protocolo n?o-cir?rgico FMSRP (Full Mouth Scalling and Root Planing), por?m, sem a utiliza??o do ultrassom. Os par?metros cl?nicos ?ndice de placa vis?vel (IPV), ?ndice de sangramento gengival (ISG), profundidade de sondagem (PS), sangramento ? sondagem (SS) e mucosa queratinizada foram avaliados no baseline e em diferentes per?odos ap?s o tratamento. Os dados n?o apresentaram distribui??o normal e o implante foi considerado a unidade amostral. Os dados foram analisados por meio dos testes de Friedman, Wilcoxon e Qui-quadrado (&#61537;=5%), utilizando o Statistical Package for Social Sciences 17.0 (SPSS). Os resultados mostraram que houve diferen?a estatisticamente significativa (p<0,05) para as vari?veis: m?dia do IPV dos implantes em ambos os grupos; m?dia do ISG dos implantes tanto no grupo teste, como controle dos implantes; PS para o grupo teste e controle e SS dentro dos dois grupos de tratamento. No entanto, n?o houve diferen?a estatisticamente significativa quando os grupos foram comparados. As vari?veis PS e SS n?o mostraram diferen?a estatisticamente significativa com nenhuma vari?vel independente de interesse para este estudo (idade, sexo, fumo, grupo de tratamento, mucosa ceratinizada nos diferentes tempos, bi?tipo peri-implantar, m?dia do IPV e ISG nos implantes). Desta forma, pode-se concluir que tanto a terapia mec?nica isolada como sua associa??o com bochechos de digluconato de clorexidina a 0,12% podem ser usados para o tratamento da mucosite peri-implantar. Al?m disso, a condi??o de higiene bucal melhorou entre o baseline e seis meses e a profundidade e sangramento ? sondagem reduziram ap?s tr?s e seis meses

Objectives: Tooth replacement therapy using endosseous implants has become an essential component of contemporary dental practice. While a plethora of factors determine clinical success, the bucco-lingual and apico-coronal dimensions of the peri-implant mucosa play an important role in both esthetics and the maintenance of peri-implant health. Studies, most of which treat mucogingival defects in the natural dentition, comparing acellular dermal matrix (ADM) and autologous subepithelial connective tissue grafts (sCTG) have shown similar clinical outcomes. The purpose of this non-inferiority trial is to determine the clinical efficacy of ADM in the augmentation of peri-implant mucosa thickness (PMT) as compared to an autologous sCTG in human adults. Methods: Twenty healthy adults treatment planned for a single tooth implant restoration in need of simultaneous peri-implant mucosa augmentation at the time of implant placement were recruited on the basis of an eligibility criteria. Patients were randomly assigned to the control group (autologous sCTG), or the experimental group (ADM allograft). Clinical measurements of mucosal thickness at the site were made with a periodontal probe and an endodontic spreader at baseline and 16 weeks post-op. These measurements were made by a masked, calibrated examiner. Gingival health, oral hygiene, wound healing and patient reported outcomes were also obtained. Mann-Whitney U tests were used to compare the mean mucosal thickness changes between the groups. Results: The mean gain in PMT was approximately 1.5mm in the control group and 0.8mm in the experimental group. When measured at 1, 3 and 5mm apical from the CEJ, only the 3mm site exhibited a difference between the groups that approached statistical significance (control: 2.08 ± 0.80mm, test: 0.83 ± 1.37mm, Mann Whitney U = 10.00, p=0.05). Changes in keratinized mucosa width, healing index and patient reported outcomes were generally similar between the two groups. Conclusions: Within the limitations of this study, both autologous sCTG and ADM appear to be adequate materials to augment PMT without sacrificing other relevant clinical parameters and/or patient related outcomes.

Uma das complicações mais importantes relacionadas com o tratamento de implante dentário é a peri-implantite. Devido a limitação pela sobreposição de estruturas da técnica periapical, nos casos da perda óssea peri-implantar nas faces vestibulares e linguais ou palatais necessita-se de um exame capaz de prover imagens em 3 dimensões para o correto diagnóstico, sendo as imagens de tomografia computadorizada por feixe cônico (TCFC) as mais indicadas. O objetivo deste estudo foi avaliar a acurácia, especificidade, sensibilidade, concordância inter e intraobservadores e determinar a influência dos artefatos na detecção dos defeitos ósseos peri-implantares simulados em mandíbulas humanas edêndulas secas. Foram utilizados dois aparelhos de TCFC com diferentes protocolos de aquisição: i-CAT Gendex CB-500(120kVp, 5mA) e ORTHOPANTOMOGRAPH OP300(90kVp, 6.3mA). Foram instalados 24 implantes dentários cilíndricos e executados dezesseis defeitos somente nas faces vestibulares, com os comprimentos que variaram de 0,5mm a 15mm. Somente cortes sagitais foram utilizados para avaliação qualitativa e quantitativa dos defeitos foi realizada por meio de Image J. Os resultados do teste de concordância intra e inter-observadores tanto nas avaliações qualitativas e quantitativas foram predominantemente fracos. Os valores de Área Sob a Curva (ASC) variaram de 0.51 a 0.72 no i-CAT Gendex CB-500; e no ORTHOPANTOMOGRAPH OP300 variaram de 0.54 a 0.75, demonstrando desempenho diagnóstico ligeiramente superior. Nas imagens obtidas em aparelho com 120kVp (i-CAT Gendex CB-500) foram observados maior contraste em relação ao aparelho 90kVp (ORTHOPANTOMOGRAPH® OP300); em aparelho com o menor kVp (OP300) formaram mais artefatos e estes, degradaram a qualidade das imagens e influenciaram o desempenho diagnóstico das TCFCs na detecção e nas mensurações de perda óssea peri-implantar. Os protocolos de aquisições diferentes podem influenciar no aumento ou redução da formação dos artefatos. / One of the most important complications related to dental implant treatment is periimplantitis. Due to the structures overlapping inherited to periapical technique, in cases of buccal and lingual or palatal bone loss in peri-implantitis, the 3 dimensions observation exam like cone beam computed tomography(CBCT) is most indicated. The objective of this study was to evaluate the accuracy, specificity, sensitivity, interand intra-observer agreement and to determine the influence of the artifacts in the detection of the peri-implant bone defects simulated in human dry mandibles. The two CBCT devices with different acquisition protocols were used in this study: i-CAT Gendex CB-500 (120kVp, 5mA) and ORTHOPANTOMOGRAPH OP300 (90kVp, 6.3mA). Twenty-four cylindrical dental implants were placed and 16 defects were prepared only on buccal faces, the defect lengths ranged from 0.5mm to 15mm. For qualitative and quantitative assessment, only sagittal slices were evaluated by the observers, using Image J software. The results of intra and inter-observer agreement tests in both assessments were generally poor. The AUC values ranged from 0.51 to 0.72 on the i-CAT Gendex CB-500; and in the ORTHOPANTOMOGRAPH OP300 ranged from 0.54 to 0.75, showing slightly higher diagnostic performance. Higher contrast was observed in the 120 kVp device\'s images (i-CAT Gendex CB-500) when compared with the 90 kVp device\'s image (ORTHOPANTOMOGRAPH® OP300). The low kVp device (OP300), formed more artifacts which degraded the image quality and influenced the CBCT diagnostic performance in the detection and measurement of peri-implant bone loss. Different CBCT acquisition protocols may influence increasing or reducing artefact formation.

No description available.

O objetivo deste estudo foi avaliar a acurácia, sensibilidade, especificidade e concordância inter e intra-observador dos exames radiográficos: radiografia periapical digital indireta (RP) por meio de placas de fósforo e tomografia computadorizada por feixe cônico (TCFC) na detecção de defeitos ósseos peri-implantares quimicamente simulados com Ácido Perclórico a 70%. 80 implantes foram instalados em blocos de costela bovina. Os implantes foram divididos em 2 grupos (grupo controle e grupo teste), em seguida o grupo teste foi dividido em 2 subgrupos (G1 e G2). O grupo G1 foi exposto a 4h de ácido causando defeitos de aproximadamente 3-4 mm de profundidade e largura <=1 mm, enquanto o grupo G2 foi exposto a 12h . Posteriormente, as amostras foram submetidas a um sistema de Radiografia digital indireta por meio de placa de fósforo (CS 7600) e a dois diferentes tomógrafos, utilizando variados protocolos (iCAT Next Generation e 3D Accuitomo 170). Os observadores avaliaram as imagens em um programa de visualização independente (OsiriX MD) utilizando a ferramenta a 3D-RMP que permite explorar cortes axiais, coronais, sagitais, parassagitais e circunferenciais simultaneamente. Nas amostras avaliadas por radiografia periapical, os valores da ASC encontrados nas amostras com defeitos ósseo menores variaram entre 0,442 a 0,534; no iCAT Next Generantion, variaram entre 0,645 a 0.828 em dois protocolos diferente. No 3D Accuitomo 170, variaram entre 0.563 a 0.904, em protocolos diferentes. No grupo com defeito ósseos maiores os resultados foram superiores. Na radiografia periapical, os valores encontrados variaram entre 0,652 a 0,771; no iCAT Next Generation, variaram entre 0,708 a 0,946 em dois protocolos diferentes e no 3D Accuitomo 170, entre 0.628 a 0.962 em 4 protocolos diferentes. A radiografia periapical foi a modalidade testada que obteve pior desempenho, especialmente no grupo de lesões menores. O protocolo de 90 kVp, FOV 4x4 cm e 1009 projeções de raios-X do 3D Accuitomo 170 foi o que obteve os valores de diagnóstico mais altos. A TCFC obteve resultados mais satisfatórios que a RP para a detecção de defeitos ósseos peri-implantares. Porém o uso da TCFC deve ser cauteloso e criterioso na hora da escolha do protocolo de aquisição adequado para cada situação. / The aim of this study was to test the accuracy, sensitivity, specificity, inter and intra-observer and area AZ values of two radiographic examinations: digital periapical radiographs and cone beam computed tomography (CBCT) in the detection of two sizes of peri-implant bone defects chemically simulated with Perchloric Acid 70%. PR and CBCT were performed in 80 dental implants installed in blocks of bovine rib. An indirect digital radiography system using smart phosphor plates (CS 7600) and two different CBCT scanners, using different protocols (iCAT Next Generation 3D Accuitomo 170) were evaluated. Observers evaluated the images in a separate DICOM viewer (OsiriX MD) using the 3D-RMP tool. This tool allows the visualization of axial, coronal, sagittal, cross-section and circumferential images. In samples evaluated by periapical radiography, the AZ values found in the samples with smaller bone defects ranged from 0.442 to 0.534; in iCAT Next Generantion, ranged from 0.645 to 0.828 in two different protocols. In 3D Accuitomo 170, ranged 0.563-0.904 in four different protocols. In the group with larger bone defect results were superior. In periapical, the values found ranged from 0.652 to 0.771; iCAT the Next Generation ranged from 0.708 to 0.946 in two different protocols and 3D Accuitomo 170, 0.628-0.962 in 4 different protocols. Periapical radiographs were tested method that had a worse performance, especially in the smaller lesions group. The protocol FOV 4x4 cm and 1009 frames of 3D Accuitomo 170 had the highest diagnostic values. The CBCT proved to be a useful imaging modality for detecting the peri-implant bone defects, with better results than PR. But the use of CBCT should be cautious and careful when choosing the acquisition protocol appropriate for each situation.

O objetivo deste estudo foi avaliar a acurácia, sensibilidade, especificidade e concordância inter e intra-observador dos exames radiográficos: radiografia periapical digital indireta (RP) por meio de placas de fósforo e tomografia computadorizada por feixe cônico (TCFC) na detecção de defeitos ósseos peri-implantares quimicamente simulados com Ácido Perclórico a 70%. 80 implantes foram instalados em blocos de costela bovina. Os implantes foram divididos em 2 grupos (grupo controle e grupo teste), em seguida o grupo teste foi dividido em 2 subgrupos (G1 e G2). O grupo G1 foi exposto a 4h de ácido causando defeitos de aproximadamente 3-4 mm de profundidade e largura <=1 mm, enquanto o grupo G2 foi exposto a 12h . Posteriormente, as amostras foram submetidas a um sistema de Radiografia digital indireta por meio de placa de fósforo (CS 7600) e a dois diferentes tomógrafos, utilizando variados protocolos (iCAT Next Generation e 3D Accuitomo 170). Os observadores avaliaram as imagens em um programa de visualização independente (OsiriX MD) utilizando a ferramenta a 3D-RMP que permite explorar cortes axiais, coronais, sagitais, parassagitais e circunferenciais simultaneamente. Nas amostras avaliadas por radiografia periapical, os valores da ASC encontrados nas amostras com defeitos ósseo menores variaram entre 0,442 a 0,534; no iCAT Next Generantion, variaram entre 0,645 a 0.828 em dois protocolos diferente. No 3D Accuitomo 170, variaram entre 0.563 a 0.904, em protocolos diferentes. No grupo com defeito ósseos maiores os resultados foram superiores. Na radiografia periapical, os valores encontrados variaram entre 0,652 a 0,771; no iCAT Next Generation, variaram entre 0,708 a 0,946 em dois protocolos diferentes e no 3D Accuitomo 170, entre 0.628 a 0.962 em 4 protocolos diferentes. A radiografia periapical foi a modalidade testada que obteve pior desempenho, especialmente no grupo de lesões menores. O protocolo de 90 kVp, FOV 4x4 cm e 1009 projeções de raios-X do 3D Accuitomo 170 foi o que obteve os valores de diagnóstico mais altos. A TCFC obteve resultados mais satisfatórios que a RP para a detecção de defeitos ósseos peri-implantares. Porém o uso da TCFC deve ser cauteloso e criterioso na hora da escolha do protocolo de aquisição adequado para cada situação. / The aim of this study was to test the accuracy, sensitivity, specificity, inter and intra-observer and area AZ values of two radiographic examinations: digital periapical radiographs and cone beam computed tomography (CBCT) in the detection of two sizes of peri-implant bone defects chemically simulated with Perchloric Acid 70%. PR and CBCT were performed in 80 dental implants installed in blocks of bovine rib. An indirect digital radiography system using smart phosphor plates (CS 7600) and two different CBCT scanners, using different protocols (iCAT Next Generation 3D Accuitomo 170) were evaluated. Observers evaluated the images in a separate DICOM viewer (OsiriX MD) using the 3D-RMP tool. This tool allows the visualization of axial, coronal, sagittal, cross-section and circumferential images. In samples evaluated by periapical radiography, the AZ values found in the samples with smaller bone defects ranged from 0.442 to 0.534; in iCAT Next Generantion, ranged from 0.645 to 0.828 in two different protocols. In 3D Accuitomo 170, ranged 0.563-0.904 in four different protocols. In the group with larger bone defect results were superior. In periapical, the values found ranged from 0.652 to 0.771; iCAT the Next Generation ranged from 0.708 to 0.946 in two different protocols and 3D Accuitomo 170, 0.628-0.962 in 4 different protocols. Periapical radiographs were tested method that had a worse performance, especially in the smaller lesions group. The protocol FOV 4x4 cm and 1009 frames of 3D Accuitomo 170 had the highest diagnostic values. The CBCT proved to be a useful imaging modality for detecting the peri-implant bone defects, with better results than PR. But the use of CBCT should be cautious and careful when choosing the acquisition protocol appropriate for each situation.

Le desserrage des tiges est une complication fréquente des plâtres avec tiges transcorticales (TP) chez les grands animaux, nécessitant souvent leur retrait prématuré avant la guérison des fractures. Les charges excessives centrées sur le cortex à l’interface os-tige proximo-externe et disto-interne causent de l'ostéolyse. En utilisant un modèle de veau nouveau-né, ce projet a évalué un nouveau système de tige-manchon et anneau integré dans un plâtre (PS) optimisé pour réduire la contrainte péri-implant et le stress à l'interface os-implant. On a émis l'hypothèse que les PS se traduiraient par une ostéolyse péri-implant moindre par rapport aux TP. Dix veaux en bonne santé, de 3 semaines d'âge, ont été implantés avec les TP ou PS dans le métacarpe droit, à raison de 2 implants par veau. Les veaux ont été observés quotidiennement pour le confort et la boiterie et ont été euthanasiés à 28 jours. Les données recueillies comprenaient les radiographies à la chirurgie et à l'euthanasie et les mesures histomorphométriques de contact os-implant sur des échantillons non-décalcifiés avec les implants in situ. Les données ont été analysées en utilisant le test de Cochran-Mantel-Haenszel, une valeur de P <0,05 a été considérée comme significative. L'épaisseur corticale était plus importante pour les implants distaux que proximaux pour les deux groupes lors de la chirurgie (P = 0,03), mais était similaire entre les groupes (P > 0,3). Les veaux avec TP ont développé une boiterie plus tôt (au jour 21) que les veaux avec PS (P = 0,04). Histologiquement, il y avait plus de contact direct os-implant cortical pour les implants PS distaux que les implants TP (P = 0,04). La jonction métaphyso-diaphysaire osseuse où les implants proximaux étaient situés est impropre aux deux systèmes; chacun a un minimum de contact os-implant et de l'ostéolyse extensive. Le système PS n'ayant pas causé une ostéolyse importante lorsque implantés dans l'os diaphysaire et peut-être une alternative convenable aux TP pour des fractures comminutives des membres distaux. / Pin loosening is a common complication of transfixation pincasts (TP) in large animals, often necessitating premature removal before fracture healing. The excessive loads centered on the proximo-external and disto-internal cortices of the bone-pin interface cause osteolysis. Using a neonatal calf model, this project evaluated a novel pin-sleeve and ring cast system (PS) optimized to decrease peri-implant strain and evenly share stress at the bone-implant interface. It was hypothesized that PS would result in less peri-implant osteolysis compared to TP. Ten, 3-week-old, healthy calves were implanted with either TP or PS in the right metacarpus, 2 implants per calf. Calves were scored daily for lameness and were euthanized at day 28. Collected data included radiographs at surgery and euthanasia and histomorphometric measures of bone-implant contact on non-decalcified specimens with the implants in situ. Data was analyzed using Cochran-Mantel-Haenszel test; a P-value <.05 was considered significant. The cortical thickness was larger for distal implants than proximal implants for both groups at surgery (P = 0.03), but were similar between groups (P > 0.3). TP calves developed lameness sooner, at day 21, than PS calves (P = 0.04). Histologically, there was more direct cortical bone-implant contact for PS distal implants than TP implants (P = 0.04). The metaphyseal-diaphyseal junction where the proximal implants were situated is unsuitable bone for either system; each had minimal bone-implant contact and extensive osteolysis. The PS system did not cause significant osteolysis when instrumented in diaphyseal bone and is a suitable alternative to TP for comminuted distal limb fractures.

Abstract Bone remodelling occurs in humans throughout life, therefore bone is continuously renewed to better respond to changes in weightbearing circumstances. Bone remodelling is extremely vulnerable during fracture healing and integration of prostheses into the surrounding bone. Bone remodelling is a complex system in which many growth factors, cytokines and enzymes, which are essential for the differentiation of osteoblasts and osteoclasts, are involved. Some widely used drugs can affect this sensitive system of remodellation in unexpected manner. Painkillers such as cyclooxygenase (COX) inhibitors have been demonstrated in animal studies to interfere with fracture healing and a few retrospective clinical studies confirm these observations. Bisphosphonates (BP), main target of which is the bone resorbing osteoclast, have been suggested to be the drug of choice to improve periprosthetic bone density and thus prevent aseptic loosening of implants. The exact mechanism of action of clodronate (CLO), a non-amino-BP, which was selected for the study, has not been clarified thus far. In order to gain a deeper understanding of the role of the COX enzyme in the differentiation of osteoblasts we studied human mesenchymal stem cell (hMSC) cultures in the presence of different COX-inhibitors; indomethacine, parecoxib and NS398, a specific COX-2 inhibitor. We used the liposome encapsulated CLO metabolite (AppCCl2p) to study in detail the mechanism of BP induced apoptosis in osteoclast. The effects of different BPs CLO, pamidronate (PAM) and zoledronic acid (ZOL), on the differentiation of osteoblasts and osteoclasts were tested in vitro. The optimal concentration for in situ CLO rinsing in clinical study was found. Finally, the effects of in situ and per oral CLO on the periimplant bone density and integration of prostheses were studied in vivo. All tested COX-inhibitors significantly inhibited osteoblast differentiation from hMSCs and stimulated the differentiation of adipocytes. It was also demonstrated that AppCCl2p inhibits mitochondrial function by a mechanism that involves competitive inhibition of ADP/ATP translocase. In the comparison of BPs, ZOL seemed to posses the properties of both non-amino- and amino-BPs and it thus belongs to a new class of BPs. Peroral and in situ CLO seemed to have different mechanisms of action. Peroral CLO delayed the integration of prosthesis to the bone and increased peri-implant osteolysis while is situ CLO accelerated integration. In conclusion, we can alter normal bone remodellation during fracture healing and prosthesis integration. On the other hand, we can also improve the circumstances for the integration of implant to the surrounding bone by in situ BP rinsing, thus creating a better environment for bone ingrowth. / Tiivistelmä Läpi elämän luustossa tapahtuu uudelleenmuotoutumista, remodelaatiota, jonka seurauksena luu pystyy paremmin vastaamaan muuttuneisiin kuormitusolosuhteisiin. Remodelaatioprosessi on hyvin haavoittuvainen murtuman luutumisen aikana sekä proteesin kiinnittyessä ympäröivään luuhun. Luun remodelaatioon osallistuvat kasvutekijät, sytokiinit ja entsyymit, jotka puolestaan ovat välttämättömiä osteoblastien ja osteoklastien erilaistumiselle. Monet lääkeaineet voivat yllättävällä tavalla vahingoittaa tätä herkkää remodelaatiosysteemiä. Kipulääkkeet, kuten syklo-oksygenaasi (COX) estäjät, voivat häiritä murtuman luutumista aikaisempien eläintöiden ja muutamien retrospektiivisten potilastutkimusten mukaan. Lisäksi bisfosfonaatit, joiden päävaikutuskohde on luuta hajoittava osteoklasti, voisivat olla lupaavia lääkkeitä myös parantamaan proteesia ympäröivän luun laatua ja siten estämään aseptista implantin irtoamista. Tutkimuksen yhtenä tarkoituksena oli selvittää klodronaatin, ensimmäisen polven typpi-ryhmää sisältämättömän bisfosfonaatin tarkka vaikutusmekanismi. Viljelemällä ihmisen luuytimen kantasoluja indometasiinia, parekoksibia tai spesifistä COX-2 estäjää NS 398:a, sisältävässä kasvatusliuoksessa selvitettiin COX-entsyymin merkitys osteoblastien erilaistumiselle. Liposomien sisälle pakattua klodronaatin metaboliittia (AppCCl2p) käytettiin tutkittaessa millä vaikutusmekanismilla klodronaatti aiheuttaa osteoklastien apoptoosin. Bisfosfonaattien; klodronaatin, pamidronaatin ja tsoledronaatin vaikutusta osteoklastien ja osteoblastien erilaistumiseen tutkittiin soluviljelmämallissa ja määritettiin kliinisessä potilastyössä paikallisesti käytettävän klodronaattiliuoksen pitoisuus. Lopuksi potilastyössä selvitettiin paikallisen klodronaattihuuhtelun ja suun kautta annostellun klodronaatin vaikutus proteesia ympäröivän luun tiheyteen ja proteesin kiinnittymiseen ympäristöönsä. Tutkimukseen valitut COX-estäjät vähensivät ihmisen kantasolujen erilaistumista osteoblasteiksi ja lisäsivät erilaistumista rasvasoluiksi. Lisäksi todettiin, että AppCCl2p estää mitokondrioissa tapahtuvaa hengitystä estämällä ADP/ATP-vaihtajan toiminnan, saaden aikaan solukuoleman. Vertailtaessa bisfosfonaatteja, tsoledronaatilla vaikutti olevan sekä ensimmäisen, että kolmannen polven (sisältää typpi-ryhmän) bispfosfonaattien vaikutuksia, joten tsoledronaatti kuuluu aivan uuteen bisfosfonaattiryhmään. Potilastutkimuksessa suun kautta ja paikallisesti reisiluun ytimeen annostellulla klodronaatilla oli täysin erilainen vaikutus. Suun kautta syötynä klodronaatti hidasti proteesin kiinnittymistä ja aiheutti osteolyysiä. Sen sijaan paikallinen klodronaatti nopeutti merkittävästi proteesin kiinnittymistä ympäröivään luuhun. Näiden tutkimustulosten perusteella voidaan olettaa, että COX-estäjät, samoin kuin peroraalinen bisfosfonaatti, voivat tahattomasti häiritä luun remodelaatiota.

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