Las fracturas son una causa importante de sufrim¬iento, discapacidad, mala calidad de vida y muerte prematura, la identificación de individu¬os con mayor riesgo ha sido motivo de gran investigación, por ello en la actualidad, con el desarrollo del test online FRAX® de la OMS, los médicos de todo el mundo pueden identificar con mayor facilidad a los pacientes con mayor riesgo de fractura. Se estudiaron historias clínicas de pacientes entre 40 y 90 años que acudieron a consulta externa de Traumatología del Hospital Nacional Daniel Alcides Carrión en el 2014, Lima - Perú, con el diseño retrospectivo, transversal descriptivo y observacional, para evaluar el Riesgo absoluto de fractura mediante la herramienta FRAX. Los datos estadísticos fueron evaluados por el sistema estadístico SPSS 22,1. Se revisaron 477 historias clínicas de los pacientes de este servicio que cumplían con criterios de inclusión ya establecidos, de los cuáles el 70,6% eran mujeres, con una edad promedio de 60,78 ± 11,52; según índice FRAX el riesgo de fractura fue bajo en 89,7%, riesgo de fractura medio de 9% y riesgo de fractura alto 1,3%. De los pacientes que presentaron riesgo alto, todos fueron del sexo femenino con edad mayor a 70 años y antecedente de padres con fractura previa.

Osteoporosis is the most common human bone disease and a growing public health problem. Worldwide, 9 million fractures due to osteoporosis occur annually. Fracture is the main burden of the disease and is linked with significant morbidity and mortality. A history of upper extremity fragility fracture is known to contribute to increased risk of subsequent fractures. In this study, we compared the estimated FRAX 10-year probability of major osteoporotic fracture and hip fracture between upper extremity (UE) fracture and non-fracture patients. In addition, we assessed differences in demographics and osteoporosis evaluation between the two groups, and we report the prevalence of lab abnormalities among UE fragility fracture patients evaluated in our fracture liaison service (FLS). A total of 243 patients from Brigham and Women’s Faulkner Hospital were recruited to participate in the study. UE fracture patients were recruited from our FLS, and UE non-fracture patients were recruited from the UE clinic. Overall 10-year probability of major osteoporotic and hip fracture was higher in upper extremity fracture patients than upper extremity non-fracture patients (19.23 versus 9.23, p <0.001 and 4.26 versus 1.54. p < 0.001 respectively). When excluding fragility fracture history, 10-year probability of major osteoporotic fracture and hip fracture were similar between upper extremity fracture and non-fracture patients (10.59 versus 9.23, p = 0.095 and 1.88 versus 1.54, p = 0.215 respectively). The proportion of osteoporosis evaluation via bone mineral density assessment was higher in upper extremity fracture patients compared to upper extremity non-fracture patients (p < 0.001). However, the proportion of upper extremity fracture patients on osteoporosis medication was low and not different than upper extremity non-fracture patients (p < 0.079). Our results highlight history of fragility fracture as an important driver in subsequent fracture risk. UE fracture and non-fracture patients harbor similar fracture clinical risk factors, with the exception of fracture history, and are similarly at risk for future hip fracture and major osteoporotic fracture. Our results suggest close osteoporosis evaluation of older upper extremity non-fracture patients is warranted.

Osteoporosis is a common skeletal disease that weakens bones and increases the risk of fractures. It affects about one half of women over the age of 60, and one third of older men. With appropriate care, osteoporosis can be prevented; and when present, it can be easily diagnosed and managed. Unfortunately, many patients with osteoporosis are not recognized or treated, even after sustaining a low-trauma fracture. Even when treatment is initiated, patients may not take medication correctly, regularly, or for a sufficient amount of time to receive the benefit of fracture risk reduction. Efforts to improve compliance and treatment outcomes include longer dosing intervals and parenteral administration. Clinical practice guidelines for the prevention and treatment of osteoporosis have been developed by the National Osteoporosis Foundation (NOF) but may not be fully utilized by clinicians who must deal with numerous healthcare priorities. We present an algorithm to help streamline the work of busy clinicians so they can efficiently provide state-of-the-art care to patients with osteoporosis.

Patients with osteoporosis have an increased risk of sustaining fractures because of the low bone mineral density (BMD) and altered bone micro-architecture which are characteristic features of the disease. Although a good correlation exists between BMD and fracture risks, many other factors influence this relationship. While there is consensus that patients with osteoporosis should be investigated and treated, the issue is much less clear for patients with osteopenia. Because osteopenia is so prevalent, it would be unrealistic to treat all patients with this condition. Therefore, there is a need to identify those patients who are at risk of sustaining a fracture and would benefit most from the available therapy. Providing treatment to the appropriate risk group would not only reduce the number of fractures, but could also reduce the adverse effects associated with treatment, as treating patients earlier could shorten the treatment time. The availability of tools to select patients at risk of fracture should change the impact of the disease.

The World Health Organization fracture risk assessment tool (FRAX) uses clinical risk factors to predict the patient's 10-yr probability of sustaining a hip or other major osteoporosis-related fracture. Inclusion of the femoral neck T-score is optional in the calculation. We evaluated the impact of including the T-score in the calculation of fracture risk and resultant treatment recommendation. We retrospectively reviewed charts of 180 white women scanned on a Hologic dual-energy X-ray absorptiometry (DXA). FRAX scores were calculated with T-scores (FRAX+) and without T-scores (FRAX-). We compared the National Osteoporosis Foundation (NOF) treatment recommendations (≥20% risk of a major osteoporotic fracture or ≥3% risk of hip fracture for osteopenic patients) between FRAX+ and FRAX- scores. Agreement between FRAX+ and FRAX- was 89.4%. Disagreement occurred in 2 distinct subgroups of patients (10.6% of cases), that is, FRAX+ scores exceeded the NOF recommended treatment thresholds and FRAX- scores did not, or vice versa. One subgroup comprised older patients with normal T-scores for whom FRAX- scores exceeded the treatment threshold. The second subgroup comprised younger patients with high body mass index (BMI) and low T-scores for whom FRAX- scores did not exceed the treatment threshold. FRAX scores generated without T-scores may lead to treatment recommendations for patients who have normal bone mineral density and no treatment recommendations for patients who have osteoporosis. T-scores should be used for optimal application of FRAX.

Ever since traditional medicine developed thousands of years ago, humans have looked to natural substances as remedies for maladies. Today, many isolation and natural product chemists have begun revisiting ancient folk medicines in an attempt to isolate the compound(s) responsible for effective treatment. In addition to the examination of traditional remedies, the secondary metabolites of many newly discovered species, especially bacteria, get tested against a wide array of pathogenic cells. Isolated from the myxobacterium Sorangium cellulosum, the secondary metabolite carolacton was discovered to be lethal to Streptococcus mutans cells transitioning to the biofilm state. This was a significant finding since S. mutans is the main causative agent of dental caries, the most prevalent chronic childhood and adolescent disease worldwide. Herein, our efforts to design, synthesize, and biologically evaluate a 16-member library of carolacton-inspired analogs is described. In addition to natural product inspired research, two projects borne from a target-oriented templated approach are also described. The first, the synthesis of the antitumor compound FRAX-1036, was completed as part of a collaboration with the Chernoff group at Fox Chase Cancer Center to provide them with more material for murine testing. The second, the synthesis of macrocycles for the formation of atomically precise membranes, was conducted using spiroligomer building blocks and unnatural amino acids to furnish a triangle-shaped macrocycle via solution and solid phase techniques. This dissertation highlights the usefulness of the techniques of diverted total synthesis and building block synthesis in organic chemistry. / Chemistry

Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-11-19T13:39:09Z No. of bitstreams: 1 CristinadeJesusSousaDissertacaoParcial2018.pdf: 780979 bytes, checksum: d8b80ee196a8840b1efaee7d6dcb18f5 (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2018-11-19T13:39:46Z (GMT) No. of bitstreams: 1 CristinadeJesusSousaDissertacaoParcial2018.pdf: 780979 bytes, checksum: d8b80ee196a8840b1efaee7d6dcb18f5 (MD5) / Made available in DSpace on 2018-11-19T13:39:46Z (GMT). No. of bitstreams: 1 CristinadeJesusSousaDissertacaoParcial2018.pdf: 780979 bytes, checksum: d8b80ee196a8840b1efaee7d6dcb18f5 (MD5) Previous issue date: 2018-07-30 / This is a quantitative, cross-sectional and descriptive study whose general objective was to evaluate the bone quality of elderly women with more than 60 years of age attending a general gynecology clinic in the Distrito Federal, through the application of the FRAX Tool. The study site was a private general gynecological clinic and the sample consisted of 147 were elderly women (60 to 90 years). For the data collection, three instruments were used: a sociodemographic questionnaire, the FRAX tool and the FRAQ-Brazil instrument. Comparisons of proportions between two independent groups were performed using Fisher's exact test. Categorical variables were described with counts and proportions. Quantitative variables of normal and asymmetric distribution were described as mean ? standard deviation and median (interquartile range) respectively. Normality was assessed by visual inspection of histograms. The R software was used in the statistical analysis of data. All probabilities of significance are bilateral and values less than 0.05 are considered statistically significant. The results obtained are found in articles 1 and 2. The research allowed an intense literature review to contribute to an understanding of which factors limit the use of the FRAX Tool, and which groups of older people should be better and more carefully analyzed for orientation. We found a mean and high risk of osteoporotic fractures assessed by applying the FRAX tool in non-elderly patients by 0.3%, in elderly patients up to 79 years old was found in 3,7% and in 45,5% of the elderly women above of 80 years. It can be concluded that the FRAX tool, despite some limitations, is important for the early identification and screening of individuals at risk of fractures due to its simplicity of application, allowing early and safe therapeutic decision making. It was also concluded that there is a significant increase in the risk of osteoporotic fractures with advancing age. / Trata-se de um estudo quantitativo, transversal e descritivo cujo objetivo geral foi avaliar a qualidade da massa ?ssea de idosas com mais de 60 anos frequentadoras de uma cl?nica de ginecologia geral no Distrito Federal, por meio da aplica??o da Ferramenta FRAX. O local do estudo foi uma cl?nica particular de ginecol?gica geral e a amostra foi constitu?da 147 mulheres idosas (60 a 90 anos). Para a coleta de dados, utilizaram-se tr?s instrumentos: um question?rio sociodemogr?fico, a Ferramenta FRAX e o instrumento FRAQ-Brasil. Compara??es de propor??es entre dois grupos independentes foram efetuadas utilizando-se teste exato de Fisher. Vari?veis categ?ricas foram descritas com contagens e propor??es. Vari?veis quantitativas de distribui??o normal e assim?trica foram descritas como m?dia ? desvio padr?o e mediana (intervalo interquartil) respectivamente. Normalidade foi avaliada com a inspe??o visual de histogramas. O software R foi utilizado na an?lise estat?stica de dados. Todas as probabilidades de signific?ncia apresentadas s?o do tipo bilateral e valores menores que 0.05 considerados estatisticamente significantes. Os resultados obtidos encontram-se nos artigos 1 e 2. A pesquisa permitiu a realiza??o de uma intensa revis?o de literatura visando contribuir para uma compreens?o de quais fatores limitam o uso da Ferramenta FRAX, e quais grupos de idosos devem ser melhores e mais cuidadosamente analisados para a orienta??o. Encontrou-se m?dio e alto risco de fraturas osteopor?ticas avaliado atrav?s da aplica??o da Ferramenta FRAX nas pacientes idosas aos 79 anos o percentual encontrado foi de 3,7% e em 45,5% nas idosas acima dos 80 anos. Pode-se concluir que a Ferramenta FRAX, apesar de algumas limita??es, ? importante para a identifica??o precoce e o rastreamento de indiv?duos com risco de fraturas, devido ? sua simplicidade de aplica??o, permitindo uma tomada de decis?o terap?utica precoce e segura. Concluiuse tamb?m que h? um aumento importante do risco de fraturas osteopor?ticas com o avan?ar da idade.

Summary: The FRAX algorithm assesses the patient’s probability of sustaining an osteoporotic fracture and can be calculated with or without densitometric data. This study seeks to determine whether in men, FRAX scores calculated without BMD, correctly identify patients with BMD-defined osteoporosis. Introduction: The diagnosis of osteoporosis is based on densitometric data, the presence of a fragility fracture or increased fracture risk. The FRAX algorithm estimates the patient’s 10-year probability of sustaining an osteoporotic fracture and can be calculated with or without BMD data. The purpose of this study is to determine whether in men, FRAX calculated without BMD, can correctly identify patients with BMD-defined osteoporosis. Methods: Retrospectively retrieved data from 726 consecutive Caucasian males, 50 to 70 years old referred to our Osteoporosis Center. Results: In the population studied, 11.8 and 25.3% had BMD-defined osteoporosis when female and male reference populations were used respectively. When the National Osteoporosis Foundation thresholds to initiate treatment are used, only 27% of patients with BMD-defined osteoporosis, but 4% with normal BMD reached/exceeded these thresholds. Lowering the threshold increased sensitivity, but decreased specificity. Conclusions: Our results suggest that FRAX without BMD is not sensitive/specific enough to be used to identify Caucasian men 50 to 70 years old with BMD-defined osteoporosis.

Fracture risk reduction is the main goal of treating osteoporosis, a condition which, in the absence of fragility fractures, is diagnosed by bone densitometry. Bone density, however, although an important factor predicting fracture risk, is not the only one and several other factors modulate the fracture risk such as the patient's age, body mass index, family history, cigarette smoking, medications and the risk of falling: most fractures are preceded by falls. When developing a treatment strategy it is therefore important to take into consideration other factors apart from bone density. Several algorithms and instruments are available for this purpose. The FRAX (Fracture Risk Assessment) tool developed under the aegis of the World Health Organization and the Garvan Fracture Risk Calculator are commonly used to estimate the patient's fracture risk. Both have advantages and limitations. It must be emphasized, however, that treatment decisions are clinical ones.

Fracture risk reduction is the main goal of treating osteoporosis, a condition which, in the absence of fragility fractures, is diagnosed by bone densitometry. Bone density, however, although an important factor predicting fracture risk, is not the only one and several other factors modulate the fracture risk such as the patient's age, body mass index, family history, cigarette smoking, medications and the risk of falling: most fractures are preceded by falls. When developing a treatment strategy it is therefore important to take into consideration other factors apart from bone density. Several algorithms and instruments are available for this purpose. The FRAX (Fracture Risk Assessment) tool developed under the aegis of the World Health Organization and the Garvan Fracture Risk Calculator are commonly used to estimate the patient's fracture risk. Both have advantages and limitations. It must be emphasized, however, that treatment decisions are clinical ones.