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QUALITATIVE ASPECTS OF ADHERENCE TO ANTIRESORPTIVE TREATMENT IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS Author: Aneta Ravingerová Supervisor: Magda Vytřísalová Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Social and Clinical Pharmacy INTRODUCTION: Compliance is using of medication in accordance with a prescription drug regimen. Qualitative aspect of compliance represents use of drugs in correct way. significantly affects treatment outcomes.Suboptimal compliance The study aim was to assess qualitative compliance with bisphosphonates (BIS)AIMS: among Czech women with osteoporosis in common clinical practice. METHODS: Data collection was performed using anonymous questionnaire in five outpatient Compliance with fivecentres in the Czech Republic from November 2012 to March 2013. dosing instructions for safe use and adequate absorption of BIS was evaluated. : A total of 363 patients were involved in the analysisRESULTS (mean age 68.9 years). once a week dosing forms ofPatients were treated with BIS - alendronate, alendronate + once a month dosing formvitamine D in a fixed combination, risedronate (N = 36.6 %) or - Only 46.6 % of respondents from weekly subgroup were compliantibandronate (N = 63.4 %). with all five dosing recommendations in monthly subgroup....

Made available in DSpace on 2017-07-21T14:35:56Z (GMT). No. of bitstreams: 1 ANA PAULA VILELA.pdf: 1282511 bytes, checksum: c10f427abee56de534f400ed156c1831 (MD5) Previous issue date: 2017-02-24 / Periodontal disease (PD) can be characterized as a chronic inflammatory disease in which there is destruction of the supporting tissues of the tooth. In its pathogenesis, the presence of a biofilm triggers a local immune-inflammatory response, with the production of pro-inflammatory mediators and cellular activation; consequently bone reabsorption and collagen degradation. Regarding the therapy of PD constant academic studies have been conducted in the search for alternative treatment. In this context, strontium ranelate (SR), drug currently used in the treatment of osteoporosis, represents a study target since it has biological properties on the bone tissue, such as effective reduction of reabsorption and increase of bone neoformation. Thus, the objective of this study was to evaluate the effect of SR on alveolar bone loss induced by the ligation method in rats. In addition, the cardiovascular safety profile of SE was ensured by the evaluation of blood pressure, heart rate and vascular reactivity. For these purposes, 30 rats (Wistar / 200-300g) were divided into three groups (n = 10 animals / group): G1) Control Group - No ligature / No treatment (placebo, 0.9% NaCl, via gavage); G2) Ligature group - With ligature / No treatment (placebo, 0.9% NaCl, via gavage); G3) Group Ligature + Strontium Ranelate - With ligation / With treatment (RE, 625mg / kg / day, via gavage). Alveolar bone loss was induced by the ligature method and the experimental time was 15 days. After this period, the animals were submitted to: (1) Morphometric quantification of alveolar bone loss; (2) Histological measurement (picrosirius) of tissue collagen; (3) Total alkaline phosphatase serum dosage and (4) Evaluation of cardiovascular parameters (blood pressure, heart rate and vascular reactivity). Comparing the means between groups using the parametric ANOVA test, followed by Tukey post hoc, performed statistical analysis. The level of significance was 5%. In the group in which the animals received SE treatment (G3) there was a significant decrease in alveolar bone loss, accompanied by a preservation of the periodontal collagen fibers. In addition, the alkaline phosphatase total levels were elevated in the G3 group. No changes were observed in the cardiovascular parameters evaluated.Although, additional studies are required, the results demonstrate that strontium ranelate represents an effective and therefore promising drug in PD therapy, reducing alveolar bone loss and tissue collagen degradation. / A doença periodontal (DP) pode ser caracterizada como uma doença inflamatória crônica na qual há destruição dos tecidos de suporte do dente. Em sua patogênese, a presença de um biofilme desencadeia uma resposta imunoinflamatória local, com a produção de mediadores pró-inflamatórios e ativação celular, consequentemente reabsorção óssea e degradação do colágeno. Sobre a terapêutica da DP, constantes estudos acadêmicos têm sido realizados na busca por alternativas de tratamento. Neste contexto, o ranelato de estrôncio (RE), fármaco atualmente empregado na terapêutica da osteoporose, representa um alvo de estudo, uma vez que possui propriedades biológicas sobre o tecido ósseo, tais como diminuição efetiva da reabsorção e aumento da neoformação óssea. Assim, o objetivo deste trabalho foi avaliar o efeito do RE sobre a perda óssea alveolar induzida pelo método da ligadura em ratos. Em acréscimo, o perfil de segurança cardiovascular do RE foi assegurado pela avaliação da pressão arterial, frequência cardíaca e reatividade vascular. Para estas finalidades, 30 ratos (Wistar / 200 - 300g) foram divididos em três grupos (n=10 animais/grupo):G1) Grupo Controle – Sem ligadura / Sem tratamento (placebo, NaCl 0,9%, via gavagem); G2) Grupo Ligadura – Com ligadura / Sem tratamento (placebo, NaCl 0,9%, via gavagem); G3) Grupo Ligadura + Ranelato de Estrôncio - Com ligadura / Com tratamento (RE, 625mg/kg/dia, via gavagem). A perda óssea alveolar foi induzida pelo método da ligadura e o tempo experimental foi de 15 dias. Após este período, os animais foram submetidos à: (1) Quantificação morfométrica da perda óssea alveolar; (2) Mensuração histológica (picrosirius) de colágeno tecidual; (3) Dosagem sérica de Fosfatase alcalina total e óssea e (4) Avaliação de parâmetros cardiovasculares (Pressão arterial, frequência cardíaca e reatividade vascular). A análise estatística foi realizada pela comparação das médias entre os grupos por meio do teste paramétrico de ANOVA, seguido de post hoc Tukey. O nível de significância foi de 5%. No grupo em que os animais receberam tratamento de RE (G3) houve uma diminuição significativa da perda óssea alveolar, acompanhada de uma preservação das fibras de colágeno do periodonto. Em acréscimo, os níveis de fosfatase alcalina total e óssea apresentaram-se elevados no grupo G3. Não foram observadas alterações nos parâmetros cardiovasculares avaliados. Embora estudos adicionais sejam necessários, o resultados demonstram que o ranelato de estrôncio representa um fármaco eficaz e portanto promissor na terapêutica da DP, reduzindo a perda óssea alveolar e degradação do colágeno tecidual.

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Os distÃrbios na articulaÃÃo temporomandibular (ATM) estÃo associados com dor inflamatÃria. O ranelato de estrÃncio à utilizado no tratamento da osteoporose. Embora o mecanismo de aÃÃo de ranelato nÃo esteja elucidado, hà provas de seu efeito analgÃsico. Investigamos a eficÃcia do Ranelato na hipernocicepÃÃo inflamatÃria induzido pelo zymosan na ATM de ratos, avaliando o envolvimento TNF-α, IL-1β, e hemeoxygenase-1. Ratos Wistar foram tratados previamente com Ranelato (0,5, 5 ou 50 mg / kg) antes da injeÃÃo de zymosan na ATM. O Teste de Von Frey foi utilizado para avaliar hipernocicepÃÃo. ApÃs a injeÃÃo de zymosan o lavado sinovial foi recolhido para a contagem de leucÃcitos e dosagem de mieloperoxidase; tecido periarticular e no gÃnglio trigeminal foram retirados para anÃlise histopatolÃgica (H & E), e dosagem dos nÃveis de TNF-α e IL-1β (ELISA). Para imuno-histoquÃmica, secÃÃes da ATM foram submetidas ao anticorpo de TNF-α e IL-1β. AlÃm disso, os ratos foram tratados com ZnPP-IX (3 mg / kg), um inibidor especÃfico da enzima hemeoxigenase-1 (HO-1), antes do Ranelato (0,5 mg / kg). AlÃm disso, Azul de Evans (5 mg / kg) foi administrado para avaliar o extravasamento plasmÃtico. Ranelato aumentou o limiar nociceptivo. Embora Ranelato nÃo foi capaz de reduzir a contagem de leucÃcitos, a atividade da mieloperoxidase, o extravasamento de azul de Evans, os nÃveis de IL-1β, imunomarcaÃÃo de IL-1β, foi eficaz na reduÃÃo dos nÃveis de TNF-α. AlÃm disso, ZnPP-IX nÃo alterou a eficÃcia do Ranelato. Ranelato parece exercer seus efeitos de reduzir nociceptivos por meio da reduÃÃo de TNF-α no gÃnglio trigeminal. AlÃm disso, o efeito anti-nociceptivo do ranelato independe de IL-1β e HO-1. / Temporomandibular joint (TMJ) disorders are associated with inflammatory pain. Strontium ranelate is used in osteoporosis. Though the mechanism of action of Ranelate is unclear, there is evidence of its analgesic effect. We investigate Ranelate efficacy in zymosan-induced TMJ hypernociception in rats evaluating TNF-, IL-1β, and hemeoxygenase-1 involvement. Wistar rats were pretreated with Ranelate (0.5, 5 or 50mg/kg) before zymosan injection in TMJ. Von Frey test was used to evaluate hypernociception. After zymosan injection synovial lavage was collected for leukocyte counting and myeloperoxidase measurement; joint tissue and trigeminal ganglion for histopathological analysis (H&E), and TNF-/IL-1β levels dosage (ELISA). To immunohistochemistry, TMJ sections were subjected to both TNF-/IL-1β antibody. Also, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before Ranelate (0.5 mg/kg). Further, Evans Blue (5 mg/kg) was administered to assess plasma extravasation. Ranelate increased the nociceptive threshold. Although Ranelate was not able to reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1β levels, and TNF-/IL-1 immunolabeling, it was effective in reducing TNF- levels. Further, ZnPP-IX did not changed Ranelate efficacy. Ranelate may achieve its nociceptive-alleviating effects through reducing TNF- levels in trigeminal ganglion. Further, the Ranelate anti-nociceptive effect is IL-1 and HO-1-independent.

Le ranélate de strontium, prescrit dans le traitement de l'ostéoporose ménopausique, possède 2 atomes de strontium stable pouvant se fixer au minéral osseux. Le strontium a un effet dissociant sur le remodelage osseux, diminuant la résorption tout en augmentant la formation. Cependant, ses effets osseux ne sont pas complètement élucidés, en particulier ses interactions avec le minéral. Chez le singe, le strontium maintient à un niveau physiologique les propriétés intrinsèques majeures du tissu osseux, que ce soit aux niveaux tissulaire global ou des unités de remodelage. Chez la femme ostéoporotique ménopausée traitée par le ranélate de strontium, les caractéristiques du cristal d'apatite sont maintenues à un niveau physiologique. Par ailleurs, quelle que soit la durée du traitement (2 à 96 mois), le strontium est toujours distribué de façon hétérogène, présent principalement dans l'os récent formé pendant le traitement, les aires osseuses contenant du strontium augmentent progressivement mais de moins en moins avec la durée du traitement. Le contenu osseux focal en strontium est stable de 2 à 60 mois puis augmente de 60 à 96 mois, et la minéralisation secondaire est maintenue à un niveau physiologique. Enfin, après 6 et 12 mois de traitement, le ranélate de strontium maintient normaux les principaux paramètres reflétant la minéralisation secondaire, et ses effets sont similaires à ceux de l’alendronate. En conclusion, le ranélate de strontium maintient une qualité normale de la minéralisation secondaire, que ce soit à court ou à long terme, et quel que soit le modèle étudié. Le ranélate de strontium maintient également la microdureté osseuse, les caractéristiques minérales et organique tissulaires, ainsi que la structure du cristal d'apatite / Strontium ranelate, a treatment of postmenopausal osteoporosis, contains 2 atoms of stable strontium which interact with bone mineral. Strontium have a dissociating effect on bone remodeling, decreasing resorption while increasing formation. However, its bone effects are not fully clarified, in particular its interactions with mineral. In monkeys, strontium maintains the major intrinsic properties of bone at a physiological level, either at the global tissue or the bone structural units levels. In postmenopausal women treated with strontium ranelate, the characteristics of apatite crystals are maintained at a physiological level. Moreover, whatever the duration of treatment (2 to 96 months), strontium is always heterogeneously distributed, mainly present in recent bone formed during treatment, bone areas containing strontium progressively increase but less and less with the duration of the treatment. Focal bone strontium content remains stable from 2 to 60 months and then increase from 60 to 96 months, and secondary mineralization is maintained at a physiological level. Finally, after 6 and 12 months of treatment, strontium ranelate maintains normal the main parameters reflecting secondary mineralization, and its effects are similar to those of alendronate. To conclude, strontium ranelate maintains a normal quality of secondary mineralization, either after a shortterm or a long-term treatment, and whatever the model studied. Strontium ranelate also maintains bone microhardness, tissular mineral and organic characteristics, as well as the structure of apatite crystals

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Die Osteoporose ist charakterisiert durch einen progressiven Verlust an Knochengewebe und ist eine der häufigsten Komplikationen des Alters. Schätzungen zufolge sind weltweit etwa 200 Millionen Menschen an Osteoporose erkrankt, dies führte auch zur Aufnahme der Osteoporose in die WHO-Liste der 10 wichtigsten Volkskrankheiten. In einer Studie aus dem Jahr 2007 wurden die jährlichen Kosten für die Folgen dieser Erkrankung in Deutschland mit 5,4 Milliarden Euro beziffert. Osteoporose bedeutet vermehrter Knochenabbau. Ursachen sind u.a. postmenopausaler Estrogenmangel, der wiederum dazu führt, dass sich die Lebenszeit der für die Knochenresorption zuständigen Osteoklasten verlängert, während die Lebenszeit der knochenproduzierenden Osteoblasten verkürzt wird. Außerdem sind die verringerten mechanischen Reize am Knochen durch fehlende körperliche Bewegung und ein endemischer Vitamin-D-Mangel, unter dem ein Großteil der Weltbevölkerung leidet, als ursächlich für das Auftreten von Osteoporose zu nennen. Ziel dieser Arbeit ist es, herauszufinden, ob eine vertikale Ganzkörpervibrationstherapie in Kombination mit einer Gabe von Strontiumranelat oder Parathormon zu einer verbesserten Knochenstruktur im osteoporotischen Rattenfemur führt. Zu diesem Zweck werden die Femora der Ratten nach Ganzkörpervibration und/oder medikamentöser Therapie mit Strontiumranelat oder Parathormon untersucht. Nach der Tötung der Ratten wird die biomechanische Stabilität des Femur einem biomechanischen Kompressionstest unterzogen. Anschließend wird der jeweilige prozentuale Gehalt von Kalzium, Phosphat und Strontiumranelat im Knochen gemessen, um den Einfluss der Vibration in Kombination mit Strontiumranelat oder PTH auf diese Parameter zu erfassen. Abschließend erfolgt die mikroradiographische Untersuchung der Knochen, um die Veränderungen der Knochenstruktur im Bereich der Kortikalis und im trabekulären Netzwerk zu erfassen. Den Ergebnissen zufolge konnte nur durch die Gabe von Parathormon eine signifikante Verbesserung der Knochenstruktur erreicht werden, die die Bruchfestigkeit der osteoporotischen Knochen signifikant erhöhte. Strontiumranelat führte in diesem Experiment zu keiner Verbesserung der Knochenqualität. Letztlich sind weitere Studien erforderlich, um effektive Dosen und Therapiezeiträume zu ermitteln. Der Vergleich der Wirksamkeit zwischen Parathormon und Strontiumranelat zeigte, dass Parathormon schneller zu Therapieerfolgen führt als eine alleinige Therapie mit Strontiumranelat. Durch die Ganzkörpervibration konnten Verbesserungen der Knochenstruktur detektiert werden. Die Kombination aus medikamentöser Therapie mit Ganzkörpervibration zeigte keine signifikanten Therapieerfolge im Vergleich zur alleinigen Therapie mit Parathormon.

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