Dissertations / Theses on the topic 'Osteoporosic fractures'

A osteoporose é uma doença de alta prevalência na população geral, e a ocorrência de fraturas se associa a grande morbi-mortalidade e impacto econômico. Na maioria dos indivíduos afetados, a osteoporose tem etiologia multifatorial, com herdabilidade estimada entre 50 e 85%, atribuível a um conjunto de variantes genéticas de pequeno efeito individual. Raramente, há casos de osteoporose associada a síndromes monogênicas, decorrentes de defeitos genéticos de grande impacto. Postula-se que indivíduos com quadros extremos de osteoporose não sindrômica possam ter causa genética mono- ou oligogênica, atribuível a variantes de impacto intermediário sobre o fenótipo, ainda pouco reconhecidas. Nos últimos anos, o avanço das tecnologias de sequenciamento permitiu o reconhecimento de novos genes associados à fragilidade óssea e atualmente possibilita a análise simultânea de múltiplos genes. Neste contexto, os objetivos deste projeto de pesquisa foram: 1) buscar genes candidatos para fragilidade óssea previamente associados a doenças Mendelianas com alto impacto na resistência óssea, fenótipos extremos de osteoporose e estudos de associação genética em escala genômica (GWAS) para osteoporose; e 2) pesquisar a presença de variantes alélicas patogênicas nestes genes candidatos em indivíduos com osteoporose grave, familiar ou idiopática. A partir de revisão sistemática, 128 genes candidatos foram selecionados para compor um painel de sequenciamento paralelo em larga escala. O sequenciamento incluiu todos os éxons e 25 pares de bases das junções íntron-éxon. Foram consideradas variantes genéticas de interesse aquelas raras (frequência alélica < 1%) e com predição de alto impacto sobre a proteína codificada. Trinta e sete indivíduos (7 famílias e 21 casos isolados) foram selecionados seguindo critérios clínicos, laboratoriais e densitométricos restritivos, excluindo-se pacientes com causas secundárias de osteoporose. A coorte foi composta por homens em 54%, a mediana de idade ao diagnóstico foi 44 anos e 86% tinham histórico de fratura. Dentre os 28 casos índices, foram identificadas 33 variantes de interesse. Após análise de segregação familiar, foi possível excluir patogenicidade de cinco destas variantes, restando 28 variantes potencialmente patogênicas, presentes em 71% da coorte. Todas as variantes foram encontradas em heterozigose, sendo 26 variantes de ponto não-sinônimas, uma deleção de 9 pares de bases, e uma grande deleção envolvendo o único éxon codificador do gene candidato GPR68. Foi encontrada uma associação de variantes em genes diferentes em 21% da coorte, incluindo uma mulher jovem com osteoporose grave e variantes em WNT1, PLS3 e NOTCH2. A análise de segregação familiar neste caso sugeriu um efeito patogênico aditivo das variantes. Vinte e cinco porcento das variantes potencialmente patogênicas foram identificadas em genes candidatos bem estabelecidos (WNT1, PLS3, COL1A1, COL1A2), e 57% se localizam em novos genes candidatos identificados inicialmente por GWAS, como NBR1 e GPR68, também associados à alteração da remodelação óssea em modelos animais. Os resultados deste trabalho dão relevância a novos genes na fisiologia da resistência óssea e indicam um papel proeminente de interações digênicas/oligogênicas em casos de osteoporose grave, familiar ou idiopática. O reconhecimento de novas vias associadas à fragilidade óssea pode levar ao desenvolvimento de novos tratamentos, e a identificação de variantes patogênicas associadas à osteoporose pode, futuramente, permitir um manejo clínico personalizado de pacientes e seus familiares
Osteoporosis is a highly prevalent disorder resulting in fragility fractures and incurring in great morbi-mortality and economic burden. In most cases, osteoporosis has a multifactorial etiology, with an estimated heritability of 50-85% attributable to a combination of several low-impact genetic variants. Rarely, cases of syndromic osteoporosis due to high-impact genetic defects are seen. It is therefore hypothesized that severe/idiopathic cases of otherwise inconspicuous osteoporosis may have a monoor oligogenic etiology due to genetic variants with an intermediate effect. During the past years, advances in molecular sequencing have revealed novel candidate genes for bone fragility, and have enabled simultaneous sequencing of multiple genes. In this context, the objectives of this research project were: 1) to identify candidate genes for bone fragility, as previously reported in association to Mendelian disorders with high impact on bone resistance, idiopathic or familial osteoporosis, and genome-wide association studies (GWAS) for bone mineral density and fragility fractures; and 2) to perform molecular analysis of these candidate genes in patients with severe, familial or idiopathic osteoporosis. Through a systematic review, 128 candidate genes were identified and included in a panel for massively parallel sequencing. Coding regions and 25-bp boundaries were captured and sequenced. Rare variants (allele frequency < 1%), with a predicted high impact on protein function were initially selected as variants of interest. Thirty-seven subjects (21 sporadic cases and 7 families) were included according to stringent criteria based on clinical and densitometric evaluation, excluding individuals with secondary osteoporosis. Males represented 54% of the cohort, median age at diagnosis was 44 years, and 84% of subjects had a history of fractures. Thirtythree variants of interest were identified initially. After familial segregation analysis, 5 variants were considered as benign in regard to bone fragility, resulting in 28 potentially pathogenic variants, all heterozygous, present in 71% of the cohort. Of these variants, 26 were nonsynonymous, there was one 9-bp deletion and one large deletion involving the only coding exon of candidate gene GPR68. An association of two or more variants in different genes was present in 21% of the cohort, including a young woman with severe osteoporosis and variants in WNT1, PLS3 and NOTCH2. Familial segregation in this case suggested an additive pathogenic effect of these variants. Twenty-five percent of potentially pathogenic variants were identified in well-established candidate genes (WNT1, PLS3, COL1A1, COL1A2), and 57% located to novel candidate genes initially identified by GWAS, such as NBR1 and GPR68, which have been previously associated to changes in bone remodeling in mouse models. These results support the involvement of GWAS genes in the pathophysyiology of osteoporosis, and indicate a prominent role for digenic/oligogenic interactions in cases of severe, familial or idiopathic osteoporosis. Recognition of new molecular pathways in the determination of bone fragility may lead to the development of new drugs, and the identification of pathogenic variants associated to osteoporosis may allow individualized clinical management of patients and their relatives

In bone field, microRNAs (miRNAs) have been described as key factors regulating bone formation, remodeling, and homeostasis. The identification of miRNAs involved in skeletal function will be essential to the development of miRNA-based therapeutic strategies for bone disorders. As with other regulatory molecules, miRNAs are frequently subject to change during the development of human diseases. In this regard, we identified a subset of miRNAs with altered expression in osteoporotic bone and demonstrate the functional involvement of some of those miRNAs in the regulation of bone formation and the pathways regulating the progression of osteoporosis. We also have depicted an overview of miRNAs in the human bone tissue and in primary bone cells. Furthermore, we have identified genetic variants in human osteoblast-related miRNAs associated with bone mineral density and this association was functionally demonstrated in bone and osteoblast samples. This work has provided evidences of the marked complexity behind this regulatory system and opens novel prospect for research and therapy.
En l’àmbit de l’estudi de l’òs, els microRNAs (miRNAs) han estat descrits com factors claus en la regulació de la formació, remodelatge i homeòstasis de l’ òs. La identificació de miRNAs implicats en la funció esquelètica és imprescindible pel desenvolupament de noves estratègies terapèutiques, basades en miRNAs, dirigides al tractament de malalties òssies. Com en el cas d’altres molècules reguladores, els miRNAs poden patir modificacions durant el desenvolupament de malalties humanes. En aquest sentit, hem identificat un grup de miRNAs amb una expressió alterada en l’òs osteoporòtic i hem demostrat la implicació funcional d’algun d’aquests miRNAs en la regulació de la formació òssia i els mecanismes pels quals es produiria l’osteoporosi. Alhora, també hem ofert una visió general dels miRNAs presents en el teixit ossi humà i en les cèl·lules òssies. També hem identificat variants genètiques dins de les seqüències de miRNAs expressats en osteoblasts, que han estat associades amb la densitat mineral òssia. A més a més, aquesta associació ha estat funcionalment demostrada en òs i osteoblasts. Aquest treball reflexa l’elevada complexitat que hi ha darrera del sistema regulador per miRNAs i obre nous camins per la recerca i la teràpia.

[Truncated abstract] The cost of managing osteoporotic fractures places a significant financial burden on the health-care system. To reduce the fracture burden, early identification of fracture risk is essential to allow early intervention. The limitations associated with dual-energy X-ray absorptiometry (DXA), such as limited sensitivity and specificity, cost, ionising radiation and accessibility, have resulted in the emergence of other technologies for assessing bone fragility. An example is the portable and non-ionising quantitative ultrasound (QUS) technology. The discriminatory power of quantitative ultrasonometry in fracture risk identification, either independently or in combination with other established risk factors, currently remains contentious. It is recommended that fracture risk assessment should not only focus on bone status, but also on the risk of falls. Additionally, it has been noted that disability arising from osteoporotic fractures, even when these fractures are not identified clinically, can translate into psychosocial symptoms and a poorer perception of health-related quality of life (HRQoL). The primary aim of the present study was to investigate if a composite model comprising: calcaneal QUS, falls risk and HRQoL assessments, can identify a group of elderly women at high risk of osteoporotic fracture from those at lower risk. One hundred and four community-dwelling women (mean age 71.3 ±5.8 years) were recruited for this study. These women underwent a series of tests that included: DXA bone mineral density (BMD) evaluation of the proximal femur and lumbar spine (L1 L4); calcaneal QUS measurement; spinal radiography; rasterstereographic back surface curvature (BSC) examination; and performance-based assessment of strength, mobility and balance. The women were classified into a `High Risk’group or a `Low Risk’ group using three separate classification criteria: i) low BMD, based on the World Health Organisation (WHO) recommended T-score of < -2.5, and⁄or a history of fragility fracture (Osteoporotic [OP] group versus Non-Osteoporotic [NOP] group); ii) presence of at least one radiographically identified prevalent vertebral fracture (Vertebral Fracture [VF] group versus Non-Vertebral Fracture [NVF] group); or iii) a history of either forearm or wrist fracture (Forearm/Wrist Fracture [WF] group versus Non-Forearm/Wrist Fracture [NWF] group)

Introdução: A prevenção das fraturas osteoporóticas passa pela identificação dos indivíduos com fatores de risco clínicos para fratura, realização criteriosa da absorciometria de raio X de dupla energia (DEXA), tratamento anti-osteoporótico e follow-up dos doentes. Criada em 2008, validada para Portugal em 2012, a ferramenta FRAX® (WHO Fracture Risk Assessment Tool) calcula o risco de fratura da anca e de fratura major a 10 anos, ao integrar múltiplos fatores de risco. A National Osteoporosis Foundation (NOF) determinou dois limiares de alto risco, ≥3% e ≥20% respetivamente, que indicam a conduta para o tratamento farmacológico da osteopororse (OP), nos EUA. A adequação desses limiares tem sido objetivo de estudo por outros autores, mas não existem estudos na população portuguesa. O objetivo principal deste estudo foi determinar qual o limiar de risco, calculado através do FRAX®, que permite identificar com elevada sensibilidade os indivíduos com alto risco de fratura da anca, em Portugal. Métodos: De agosto a novembro de 2012, foi realizado um questionário e colheita de dados do processo clínico, de pacientes com pelo menos 50 anos, com fratura não traumática da extremidade proximal do fémur, internados no Serviço de Ortopedia do Hospital Pêro da Covilhã, do Hospital Sousa Martins e do Hospital Amato Lusitano. O risco de fratura da anca e o de fratura major foi calculado para cada paciente, através do FRAX® clínico (sem densidade mineral óssea - DMO) aferido para a população Portuguesa. Analisámos os limiares de risco FRAX® correspondentes a uma sensibilidade de 95% e 80% para a fratura incidente da anca. Resultados: Foram incluídos 138 doentes com fratura não traumática da anca. A média de idade foi 83,5±7,4 anos (81,2% mulheres). Os fatores de risco mais prevalentes foram: sexo feminino, idade superior a 65 anos, antecedentes pessoais e familiares de fratura de fragilidade e as causas de OP secundária. 91,2% dos doentes nunca tinham realizado uma DEXA e 89,8% não tinham realizado previamente medicação para a prevenção de fraturas. Os limiares de risco de FRAX® clínico de fratura da anca com sensibilidade de 80% e 95% para a fratura incidente da anca foram ≥5,5% e ≥3%, respetivamente. Conclusões: Identificámos os limiares adequados de alto risco para fratura osteoporótica da anca do instrumento FRAX® clínico numa população Portuguesa. Estes têm uma importante aplicação na prática clínica, pois permitem a melhor identificação dos indivíduos em risco, para seleção criteriosa dos que devem realizar ou não DEXA e tratamento farmacológico.
Introduction: The prevention of osteoporotic fractures involves the identification of the individuals with clinical risk factors for fracture, judicious performing of dual-energy x-ray absorptiometry (DXA), anti-osteoporotic treatment and patients’ follow-up. Created in 2008, validated for Portugal in 2012, the FRAX® tool (WHO Fracture Risk Assessment Tool) gives the 10-year probability of hip and major fracture, integrating multiple risk factors. The National Osteoporosis Foundation (NOF) determined two thresholds of high risk, ≥ 3% and ≥ 20% respectively, which indicates the treatment intervention of the OP, in USA. The adequacy of these thresholds has been the object of studies by other authors, but there aren’t any studies regarding the portuguese population. The main objective of this study was to determine the risk threshold, calculated using the FRAX® tool, which allows high sensitivity to identify individuals at high risk of hip fracture, in Portugal. Methods: From August to November 2012, a questionnaire and data collection from clinical process were performed to patients at least 50 years old, with nontraumatic hip fracture, admitted to the Orthopedics Service in Hospital Pêro da Covilhã, Hospital Sousa Martins and Hospital Amato Lusitano. The risk of hip fracture and the one of major fracture were calculated for each patient using the clinical FRAX® (without bone mineral density - BMD) measured for the Portuguese population. We analyzed the thresholds for risk FRAX® corresponding to a sensitivity of 95% and 80% for the incident hip fracture. Results: There were included 138 patients with non-traumatic hip fracture. The mean age was 83.5± 7.4 years (81.2% women). The most prevalent risk factors were: female gender, age over 65 years old, personal and parental history of fragility fracture and causes of secondary OP. 91.2% of patients had never performed DXA and 89.8% hadn’t previously made anti-osteoporotic treatment. The thresholds for high risk of hip fracture, by clinical FRAX®, with a sensitivity of 80% and 95% for the incident hip fracture were ≥5,5% and ≥3%, respectively. Conclusions: We identified appropriate thresholds at high risk for osteoporotic hip fracture, using FRAX® tool in the Portuguese population. These have an important application in clinical practice, as it allows a better identification of individuals at risk for careful selection of those who should perform DEXA and pharmacological treatment.

Introducció L'any 1990 es van produir 1,6 milions de fractures de maluc a tot el món i s'estima que aquesta xifra augmentarà a 6 milions l'any 2050. A la Unió Europea es produeixen 600.000 fractures de maluc a l'any, aproximadament, amb un cost global anual de 13.000 milions d'Euros. La incidència a Espanya és de 517 casos per cada 100.000 habitants i per any. L'edat mitjana de 82 anys i un 78% dels pacients són de sexe femení. Els objectius del tractament de la fractura de maluc són preservar la vida i aconseguir una recuperació funcional que permeti el pacient integrar-se de nou en el seu medi habitual. Però, en aquests pacients, la taxa de mortalitat s'eleva durant el primer any d'un 8,4% a un 36%. A l'any de la fractura el 50% presenten dificultats per caminar, el 38-39% presenten dificultat per fer transferències i el 17-19% presenten dificultats per a l’higiene. Fins a un 90% dels pacients presenten múltiples comorbiditats, entre les quals la malaltia pulmonar obstructiva crònica, la demència, la hipertensió arterial, la patologia cardíaca isquèmica i la diabetis són les més comunes. Les característiques d'aquests pacients, ancians i amb múltiples comorbiditats, va fer sorgir la idea de proporcionar-los una atenció compartida entre cirurgians ortopèdics i geriatres. Aquesta idea inicial ha evolucionat a la tendència actual d'implementar unitats de ortogeriatria que integrin un tractament multidisciplinari. En aquest model a geriatres i traumatòlegs se sumen també anestesistes, rehabilitadors, fisioterapeutes, infermeres i nutricionistes, entre d'altres. Objectius L'objectiu principal d'aquesta tesi doctoral és determinar la demora per a intervenció quirúrgica dels pacients amb fractura de fèmur proximal després de la implementació d'una unitat de ortogeriatria. Els objectius secundaris són determinar el temps d'estada hospitalària, la mortalitat intrahospitalària i als 30 dies, i els reingressos que es produeixen per complicacions mèdiques i traumatològiques. Material i mètodes Durant l'any 2013 (juny-desembre), 2014 i 2015, van ingressar al nostre servei 534 fractures de maluc, de manera consecutiva. Mentre que en els anys 2011, 2012 i 2013 (gener-maig), quan encara no existia la Unitat de Traumatologia Geriàtrica (UTG) van ingressar 501. Les dades recollides prospectivament en el segon període, després de la implementació de la UTG, han estat comparats amb les dades dels pacients que van ingressar en el primer període. Resultats La demora mitjana per a ser intervingut quirúrgicament prèviament a la implementació de la UTG va ser de 2,27 dies (DE = 2,35), mentre que posteriorment va ser de 1,84 (DE = 1,73). (P = 0,0004). L'estada mitjana prèviament a la implementació de la UTG va ser de 11,39 dies (DE = 9,05), mentre que posteriorment va ser de 10,08 (DE = 5,43). (P = 0,0024). La mortalitat en els primers 30 dies després de la fractura de maluc, prèviament a la implementació de la UTG va ser del 7,7%, mentre que posteriorment va ser de l'4,8%. (P = 0,027). Conclusió La implementació d'una unitat de ortogeriatria, per al tractament dels pacients amb fractura de fèmur proximal, que inclou un conjunt de mesures entre les que destaquen la introducció de circuits ràpids de tractament, tractament multidisciplinari integrat i protocols de rehabilitació primerenca postoperatòria, ha permès disminuir de 2,27-1,84 dies el temps de demora mitjà per ser intervingut quirúrgicament després de l'ingrés. El temps d'estada hospitalària s'ha reduït en un temps mitjà d'un dia. La mortalitat dels pacients als 30 dies s'ha reduït en un 2,9%. Els reingressos per complicacions mèdiques o quirúrgiques no s'han incrementat.
Introducción En el año 1990 se produjeron 1,6 millones de fracturas de cadera en todo el mundo y se estima que esa cifra aumentará a 6 millones en el año 2050. En la Unión Europea se producen 600.000 fracturas de cadera al año, aproximadamente, con un coste global anual de 13.000 millones de Euros. La incidencia en España es de 517 casos por cada 100.000 habitantes y por año. La edad media de 82 años y un 78% de los pacientes son de sexo femenino. Los objetivos del tratamiento de la fractura de cadera son preservar la vida y conseguir una recuperación funcional que permita al paciente integrarse de nuevo en su medio habitual. Pero, en estos pacientes, la tasa de mortalidad se eleva durante el primer año de un 8,4% a un 36%. Al año de la fractura el 50% presentan dificultades para caminar, el 38-39% presentan dificultades para realizar transferencias y el 17-19% presentan dificultades para el aseo. Hasta un 90% de los pacientes presentan múltiples comorbilidades, entre las que la enfermedad pulmonar obstructiva crónica, la demencia, la hipertensión arterial, la patología cardiaca isquémica y la diabetes son las más comunes. Las características de estos pacientes, ancianos y con múltiples comorbilidades, hizo surgir la idea de proporcionarles una atención compartida entre cirujanos ortopédicos y geriatras. Esa idea inicial ha evolucionado a la tendencia actual de implementar unidades de ortogeriatría que integren un tratamiento multidisciplinar. En este modelo a geriatras y traumatólogos se suman también anestesistas, rehabilitadores, fisioterapeutas, enfermeras y nutricionistas, entre otros. Objetivos El objetivo principal de esta tesis doctoral es determinar la demora para intervención quirúrgica de los pacientes con fractura de fémur proximal tras la implementación de una unidad de ortogeriatría. Los objetivos secundarios son determinar el tiempo de estancia hospitalaria, la mortalidad intrahospitalaria y a los 30 días, y los reingresos que se producen por complicaciones médicas y traumatológicas. Material y métodos Durante el año 2013 (Junio-Diciembre), 2014 y 2015, ingresaron en nuestro servicio 534 fracturas de cadera, de forma consecutiva. Mientras que en los años 2011, 2012 y 2013 (Enero-Mayo), cuando todavía no existía la Unidad de Traumatología Geriátrica (UTG) ingresaron 501. Los datos recogidos prospectivamente en el segundo periodo, tras la implementación de la UTG, han sido comparados con los datos de los pacientes que ingresaron en el primer periodo. Resultados La demora media para ser intervenido quirúrgicamente previamente a la implementación de la UTG fue de 2,27 días (DE=2,35), mientras que posteriormente fue de 1,84 (DE=1,73). (p=0,0004). La estancia media previamente a la implementación de la UTG fue de 11,39 días (DE=9,05), mientras que posteriormente fue de 10,08 (DE=5,43). (p=0,0024). La mortalidad en los primeros 30 días tras la fractura de cadera, previamente a la implementación de la UTG fue del 7,7%, mientras que posteriormente fue del 4,8%. (p = 0,027). Conclusión La implementación de una unidad de ortogeriatría, para el tratamiento de los pacientes con fractura de fémur proximal, que incluye un conjunto de medidas entre las que destacan la introducción de circuitos rápidos de tratamiento, tratamiento multidisciplinar integrado y protocolos de rehabilitación temprana postoperatoria, ha permitido disminuir de 2,27 a 1,84 días el tiempo de demora medio para ser intervenido quirúrgicamente tras el ingreso. El tiempo de estancia hospitalaria se ha reducido en un tiempo medio de un día. La mortalidad de los pacientes a los 30 días se ha reducido en un 2,9%. Los reingresos por complicaciones médicas o quirúrgicas no se han incrementado.
Introduction In 1990, there were 1.6 million hip fractures worldwide. This number is expected to reach 6 million by 2050. In the European Union, osteoporosis causes approximately 600.000 hip fractures per year. The annual estimated economic burden for healthcare systems is 13.000 million Euros. The incidence of hip fractures in Spain is 517 cases per 100.000 inhabitants and year. The average age is 82 years and 78% are women. The goal of hip fracture treatment is to return the patient to preoperative levels of function, facilitating return to pre-fracture residence and supporting long-term wellbeing. Mortality rates in hip fracture patients rise from 8.4 to 36% in the first year after surgery. One year after the fracture, 50% have difficulties in walking, 38-39% are not able to transfer from a bed to a chair and 17-19% require aids for bathing and grooming. Up to 90% of patients have several comorbidities. Commonly, these include chronic obstructive pulmonary disease, dementia, high blood pressure, ischemic heart disease, and diabetes. Elderly patients with several comorbidities could benefit from shared care approaches provided by orthopedic surgeons and geriatricians. This cooperation has triggered the current trend of implementing orthogeriatric units that integrate multidisciplinary teams. In this model, several disciplines, besides surgeons and geriatricians, are involved in the care of the patients including anesthesiologists, physical therapists, nurses, and nutritionists. Objectives The main objective of this study is to determine the delay for surgical intervention of patients with proximal femur fracture after the implementation of an orthogeriatric unit. Secondary objectives are to determine the length of hospital stay, in-hospital and 30-day mortality, and readmissions resulting from medical and trauma complications. Material and methods During 2013 (June-December), 2014, and 2015, 534 consecutive hip fractures were treated in our hospital. While in 2011, 2012, and 2013 (January-May), before the orthogeriatric unit (OGU) was created, 501 hip fractures were treated. Data collected prospectively in the second period, after the implementation of the OGU, have been compared with the first period data. Results The mean delay to undergo surgery before the implementation of the OGU was 2.27 days (SD = 2.35), compared to 1.84 (SD = 1.73). (p = 0.0004) for the second period. The average in-hospital stay before the implementation of the OGU was 11.39 days (SD = 9.05), compared to 10.08 (SD = 5.43). (p = 0.0024) after the orthogeriatric model of care was established. 30-day mortality rate after hip fracture, before OGU implementation, was 7.7%, and 4.8% afterward. (p = 0.027). Conclusion The implementation of an orthogeriatric unit for the treatment of patients with a hip fracture which requires a series of measures including the introduction of fast treatment circuits, integrated multidisciplinary treatment, and early postoperative rehabilitation protocols, has allowed a decrease from 2.27 to 1.84 days in the average time to surgery after admission. The length of hospital stay was reduced by an average time of one day. 30-day mortality was reduced by 2.9%. Readmissions for medical or surgical complications did not increase.

Thesis (M.S.M.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
OBJECTIVE: Prior studies examining the association of warfarin use and osteoporotic fractures have found conflicting results and have had methodological problems, such as confounding by indication and confounding by duration of warfarin use. Thus, we studied the association of warfarin use with fractures at the hip, spine and wrist, among older men and women with atrial fibrillation recruited from the general population, using rigorous statistical tools to overcome challenges faced by prior studies. METHODS: We included men and women ≥65 years with incident atrial fibrillation, without history of fracture, followed between 2000-2010 from The Health Improvement Network (THIN). Long-term warfarin use was defined in two ways: 1) warfarin use ≥ 1year; 2) warfarin use ≥3 years. Non-use was defined as no use of warfarin over the follow-up period. Propensity scores (PS) for warfarin use were calculated using logistic regression with long-term use of warfarin as the dependent variable and age, sex, body mass index (BMI), history of multiple falls, deep venous thrombosis, pulmonary embolism, heart failure, neuropsychiatric impairment, hyperthyroidism, estrogen use, beta blockers, corticosteroids, bisphosphonates, smoking and alcoholism as independent variables. Each warfarin user was then matched by PS to a non-user by the “greedy matching” method. Incidence rates were calculated for warfarin users and non-users. The association between long-term warfarin use and risk of hip, spine and wrist fractures was evaluated using Cox-proportional hazards models. RESULTS: Incidence rates of hip fracture were 5.21 and 6.20 per 1000 person-years among subjects with warfarin use >1 (n=20,346) and >3 (n=11,238) years, respectively. The hazard ratios of hip fracture for warfarin use >1 and >3 years were 1.08 (95% CI 0.87, 1.35) and 1.13 (95% CI: 0.84, 1.5), respectively. Similar findings were observed between warfarin use and risk of spine or wrist fracture. CONCLUSIONS: Long-term use of warfarin among older adults with atrial fibrillation is not associated with increased risk of osteoporotic fractures and thus, does not necessitate additional surveillance or prophylaxis.
2031-01-01

Orientador: Lúcia Helena Simões da Costa Paiva
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-27T21:42:31Z (GMT). No. of bitstreams: 1 Bastos-Silva_Yasmin_M.pdf: 1080942 bytes, checksum: 7599dbea7c337dddf84a74226180fc92 (MD5) Previous issue date: 2015
Resumo: O risco de fratura osteoporótica pode ser avaliado clinicamente baseado em fatores clínicos e pela densidade mineral óssea (DMO), entretanto esses parâmetros não são bons preditores do risco de fratura. Recentemente, o Brasil foi incluído no instrumento fracture risk assessment tool- FRAX-BRASIL, porém seu uso tem sido limitado na prática clínica. OBJETIVO: Avaliar o grau de concordância entre o risco de fratura em 10 anos calculado pelo FRAX-BRASIL com e sem densitometria em mulheres brasileiras na pós-menopausa. MÉTODO: Realizou-se um estudo de corte transversal no período de novembro de 2014 a fevereiro de 2015, com 402 mulheres em acompanhamento no Ambulatório de Menopausa do Hospital da Mulher Prof. Dr. José Aristodemo Pinotti em Campinas-SP. Foram incluídas mulheres com 40 anos ou mais, em amenorreia há pelo menos 12 meses e com exame de densitometria óssea prévio a qualquer tratamento medicamentoso para osteopenia ou osteoporose. As mulheres foram entrevistadas por um pesquisador durante a consulta de rotina, na qual foram coletadas informações sobre fatores de risco necessários para o questionário FRAX-BRASIL e dados da densitometria óssea. Os dados obtidos foram inseridos na plataforma online FRAX-BRASIL, em que foi calculado o risco para uma fratura maior e de quadril, utilizando-se somente os fatores de risco clínicos e o risco incluindo valores de DMO do colo do fêmur em g/cm2. ANÁLISE ESTATÍSTICA: Para análise do grau de concordância entre os riscos de fraturas com e sem densitometria óssea foi utilizado o coeficiente de correlação intraclasse (ICC). O Teste de Mann-whitney foi utilizado para comparação entre as médias do risco de fratura calculado com e sem DMO; para comparação entre as frequências de alto risco calculadas com e sem DMO foi utilizado o Teste de comparação entre duas proporções. Para análise da associação entre as variáveis clinico/demográficas e a variação do risco de fratura foi utilizada a análise de regressão linear. O nível de significância adotado foi <0,05. RESULTADOS: A probabilidade de fratura em 10 anos calculada pelo FRAX-BRASIL para fratura de quadril e para fratura maior somente pelos fatores de risco clínicos foi de 0,84% ±1,92 e 4,03% ±2,98 e com DMO foi de 0,83% ±1,76 e 4,05% ±2,98 respectivamente. O coeficiente de correlação intraclasse entre o FRAX-BRASIL com e sem DMO foi de 0,76 (IC95% 0,716-0,799) para uma fratura maior e de 0,644 (IC95% 0,583-0,698) para fratura de quadril. Ao avaliar as mulheres utilizando o FRAX com DMO 0,75% e 5,22% excederam os limiares de alto risco para fratura maior e de quadril, respectivamente. Sem o acréscimo da densidade óssea 1% e 11,44% apresentaram alto risco para fratura maior e de quadril, respectivamente. Dessa forma a recomendação de tratamento foi concordante entre o FRAX com e sem DMO em 99,75% dos casos de alto risco de fratura maior e de 93,78% para o quadril. Os fatores associados a menor variação FRAX com e sem foram maior idade, menor DMO, menor T-score e ausência de fratura previa tanto para fratura maior como para quadril. O menor IMC esteve associado a menor variação do FRAX apenas para fratura maior. CONCLUSÃO: O risco de fratura maior ou de quadril foi baixo na população estudada. O FRAX-BRASIL apresentou alta concordância para estimar o risco de fratura maior e concordância moderada para fratura de quadril apresentando uma estimativa de risco para fratura semelhante com ou sem DMO em nossa população
Abstract: The risk of osteoporotic fracture can be clinically evaluated based on clinical factors and by the bone mineral density (BMD), but these parameters are not good predictors of fracture risk. Recently, Brazil was included in the fracture risk assessment tool- FRAX-BRAZIL, but its use has been limited in clinical practice. GOAL: To evaluate the degree of correlation between the degree of correlation between the risk of fracture in 10 years calculated by FRAX-BRAZIL with and without densitometry in Brazilian postmenopausal women. METHODS: A cross-sectional study was conducted with 402 women followed up at the Menopause Ambulatory at the Women's Hospital Prof. Dr. José Aristodemo Pinotti in Campinas-SP. Women were included with 40 years or more in amenorrhea for at least 12 months and with bone densitometry exam prior to any drug treatment for osteopenia or osteoporosis. A researcher interviewed the women during a routine visit, where information about risk factors necessary for the FRAX-BRAZIL questionnaire and data of bone densitometry were collected. The collected data were inserted on the online platform FRAX-BRAZIL where the risk for major fractures and of the hip using only clinical risk factors and the risk including femoral neck BMD values in g / cm2. STATISTICAL ANALYSIS: To analyze the degree of correlation between the risk of fractures with and without bone densitometry was used the intraclass correlation coefficient (ICC). The Mann-Whitney test was used to compare the averages of fracture risk calculated with and without BMD; to compare the frequencies of high risk calculated with and without BMD was used the compare Test between two proportions. For analysis of the association between clinical / demographic variables and the change of the fracture risk was used linear regression analysis. The significance level was <0.05. RESULTS: The fracture probability calculated in 10 years by using the FRAX-BRAZIL for hip fracture and major fracture only by clinical risk factors was 0.84% ± 1.92 and 4.03 ± 2.98% and BMD was 0.83% ± 1.76 and 4.05 ± 2.98%, respectively. The intraclass correlation coefficient between the FRAX-BRAZIL with and without BMD was 0.76 (IC95% 0.716-0.799) for a major fracture and 0.644 (IC95% 0.583-0.698) for hip fracture. When evaluating women using FRAX with BMD 0.75% and 5.22% exceeded the high-risk thresholds for major and hip fracture, respectively. Without the increase of the bone density 1% and 11.44% presented high risk for major fractures and of hip, respectively. Then the treatment recommendation was consistent between the FRAX with and without BMD in 99.75% of cases of high risk of major fracture and 93.78% for the hip. Factors associated with less variation FRAX with and without were older, lower BMD, lower T-score, and no previous fracture both for major fracture as to hip fracture. The BMI was associated with lower variation in the FRAX only to major fracture. CONCLUSION: The risk of major fracture or of the hip was low in the study population. The FRAX-BRAZIL presented a high correlation to estimate the risk of major fractures and moderate agreement for hip fracture presenting a risk estimate for similar fracture with or without BMD in our population. The FRAX-BRAZIL presented a high correlation to estimate the risk of major fractures and moderate correlation for hip fracture presenting a risk estimate for similar fracture with or without BMD in our population
Mestrado
Fisiopatologia Ginecológica
Mestra em Ciências da Saúde

Thesis (Ph. D.)--West Virginia University, 2001.
Title from document title page. Document formatted into pages; contains xi, 211 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 171-186).

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.

Low dual energy X-ray absorptiometry (DXA) measured bone mineral density (BMD) is used as an indicator of reduced bone strength and increased risk of fracture. BMD is widely used to identify patients for fracture prevention treatment. However, many fracture patients are not osteoporotic and would not have been identified by BMD screening. Also, BMD screening vastly overpredicts the number of patients who will progress to fracture. In summary, there is a need to improve explanation and prediction of femoral fracture. The overall aim of this thesis was to develop a finite element (FE) methodology that can explain (better than BMD) femoral fractures. An additional aim was to develop a novel experimental methodology, computed tomography (CT)-based digital volume correlation (CT-DVC). This method measures internal strain and fracture and served as validation for the FE methodology. The study included three groups of femur specimens; Group 1: 15 cadavers served as non-fracture controls, Group 2: 14 patients who had suffered a femoral fracture and Group 3: 13 patients scheduled for arthroplasty due to osteoarthritis served as a second non-fracture control group. The correlation of FE-predicted fracture load with in-vitro testing of cadaveric femurs was superior to that of BMD predictions (R2 = 0.77 and R2 = 0.59). Also, the match between CT-based FE models and the experimental observations was reasonably good (73% match) whereas BMD is unable to explain the fracture type. FE-predicted fracture types matched 13 of 14 patient-specific clinical fractures. Including bone quality and load (fall) direction, FE explained many of the clinical fractures that BMD was unable to explain and critical fall directions were identified. FE predicted lower strength of the fracture group which was associated with smaller sizes of anatomical parameters. Also the CT- DVC method demonstrated consistent results and was deemed to have great potential for a wide range of orthopaedic applications.

OBJECTIVE:To compare and contrast patients that receive treatment following an osteoporotic fracture to those patients that do not. METHODS:Data were taken from the Medical Expenditures Panel Survey (MEPS). Subjects who reported a wrist, vertebral, or hip fracture were identified. Prescription data were assessed for these subjects and two groups were identified: those who received treatment following a fracture and those who did not. RESULTS:The final sample consisted of n=129 subjects. Of these subjects, only 38% received treatment following an osteoporotic fracture. The only variable showing significant effects on treatment were type of insurance coverage. There was evidence of a relationship for other variables: race, inability to obtain necessary prescription medicines, family income, vertebral fracture and patient's perceived health.CONCLUSIONS: Overall treatment rates following a fracture remain low. Substantial efforts should be made to close the gap between guideline recommendations and clinical practice.

Bone is refractory to most conventional biochemical Procedures. However because it is now possible to cut sections (e. g. lopm) of fresh, undemineralized adult bone, this tissue can be analyzed by suitably modified methods of quantitative cytochemistry. A new substrate for assaying hydroxyacyl dehydrogenase activity demonstrated that bone cells may use fatty acids as a major source of energy: detailed analysis of the activities of key enzymes indicated that the paradox of ‘aerobic glycolysis’ of bone could be explained by fatty acid oxidation satisfying the requirements of the Krebs' cycle and directing the conversion of pyruvate to lactate The influence of glucose 6-phosphate dehydrogenase (G6PD) activity in aerobic glycolysis has been considered. The inverse relationships between this activity and that of Na-K-ATPase led to the development of a new method for the latter, based on a new concept in cytochemistry ('hidden-capture' procedure). A major feature of fracture-healing is increased periosteal G6PD activity. The association with the vitamin K cycle has been investigated by feeding rats with dicoumarol which not only inhibited bone-formation but also G6PD activity. The stimulation of this activity in fracture-healing has been linked with ornithine decarboxylase (ODC) activity, for which a new method has been developed. Rats deficient in pyridoxal phosphate (cofactor for ODC) had decreased G6PD responses and also appeared to become osteoporotic. Studies on osteoporotic fractures in the human showed the presence of relatively large apatite crystals close to the fracture-site, and disorganized glycosaminoglycans (demonstrated by the new method of ‘induced birefringence’).

Abstract The aim of this study was to examine lifestyle risk factors for low bone mass, falls and fractures, and to determine the effect of 30-month exercise trial on bone mass, balance, muscle strength and gait in elderly women. Reliability of an inclinometric method for assessing postural sway was evaluated. Data on risk factors, falls and fractures were collected by questionnaires, and calcaneus and radius bone mass were measured from 1,222 women. Lifetime physical activity, low occupational physical activity, type 2 diabetes, hypertension, hormone replacement, thyroid hormone and thiazide use were associated with increased bone mass, while low current physical activity, high coffee intake and late menarche were associated with low bone mass in lean women. Factors associated with fractures were: low lifetime habitual physical activity, diabetes, living alone and calcaneum bone mass. One hundred and sixty women with low femoral neck bone mass were randomly assigned to the exercise group (n = 84) or to the control group (n = 76). The outcomes included radius, proximal femur and calcaneus bone mass, postural sway, muscle strength, gait speed and endurance. Bone mineral density (BMD) at proximal femur decreased in the control group, while no change occurred in the exercise group. Mean trochanter bone mineral content (BMC) decreased more in the control group. The women in the exercise group improved their performance in walking speed and endurance, body sway and leg strength compared to the control group. There were six falls that resulted in fractures in the exercise group and 16 in the control group. The inclinometric method proved to be reliable. In conclusion, lifestyle factors are determinants of bone mass in lean elderly women. Long-term exercise has a site-specific effect on BMC but not on BMD in elderly women. Weight-bearing exercise can modify risk factors for fractures, and may even prevent fall-related fractures in elderly women.

O objetivo deste estudo foi determinar se a variação genética no gene do receptor P2X7 está associada com a diminuição da densidade mineral óssea e o risco de osteoporose em pacientes acima de 50 anos de idade com fratura de tornozelo. Foi realizado um estudo diagnóstico Nível I. Os pacientes acima de 50 anos com fratura de tornozelo submetidos ao tratamento cirúrgico foram divididos em dois grupos após o resultado da densitometria óssea: o grupo de estudo com osteopenia (T score entre -1 e -2,5) ou osteoporose (T score <= -2,5) e o grupo controle com valores de normalidade (com T score >= -1). Os critérios de exclusão foram alterações que levam à osteoporose secundária. Os pacientes foram genotipados para 15 polimorfismos de nucleotídeo único (SNPs) não sinônimos dentro do receptor P2X7 (numerados de 1 à 15) obtidos a partir da saliva. Avaliamos 121 pacientes com fratura de tornozelo, sendo 56 do grupo controle e 65 do grupo de estudo. Todos os pacientes eram sedentários, não utilizavam nenhum medicamento para tratamento de osteoporose, não eram tabagistas e sofreram trauma de baixa energia. A análise agrupada das alterações dos SNPs demonstrou que se o gene tem 3 ou mais variantes de SNPs (36,4% dos 121 pacientes), dos 15 possíveis, ele está alterado com repercussão clínica relacionada à perda ou ganho de função do gene. E ao analisar as alterações dos SNPs, individualmente, os resultados sugerem que: os SNPs 1,4,14 e 15 são variantes de perda de função; SNPs 5 e 10 são descritos como variantes de perda de função; entretanto, não têm influência na nossa população; SNPs 11 e 13 são variantes de perda de função e não ganho de função, como descrito na literatura; e SNP 12 foi associado à perda de função em nossa população. Podemos ressaltar como limitações do nosso estudo o fato de nos concentramos principalmente em polimorfismos não sinônimos que não cobrem toda a variação genética em P2X7 e no número pequeno de participantes quando comparados com a literatura mundial. Em contrapartida, um dos pontos fortes do nosso estudo é ser o primeiro a avaliar o P2X7 na população brasileira, que é bastante heterogênea do ponto de vista genético devido à nossa miscigenação, quando comparado com os outros estudos que avaliaram a população do norte da Europa, que é mais homogênea geneticamente. Em conclusão, o polimorfismo do SNP 12 em P2X7 está associado à densidade mineral óssea e risco de fraturas de tornozelo
The purpose of this study was to determine whether a genetic variation in the P2X7 receptor gene is associated with reduced bone mineral density and the risk of osteoporosis in patients over 50 years of age with ankle fractures. A Level-1 diagnostic study was conducted. Patients over 50 years of age with ankle fractures who had undergone surgical treatment were divided into two groups following the result of a bone densitometry: a study group with osteopenia (bone mineral density T score between -1 and -2.5) or osteoporosis (bone mineral density T score <= -2.5) and the control group with normal values (bone mineral density T score >= -1). Exclusion criteria were alterations that led to secondary osteoporosis. Patients were genotyped for 15 nonsynonymous single nucleotide polymorphisms (SNPs) within the P2X7 receptor (numbered from 1 to 15) obtained from saliva. We evaluated 121 patients with ankle fractures, 56 being from the control group, and 65 from the study group. All patients were sedentary, did not take any medication for the treatment of osteoporosis, did not smoke, and had suffered a low-impact trauma. The grouped assessment of the SNP alterations showed that if a gene has three or more SNP variants (36.4% of the 121 patients), out of the 15 possibilities, it is altered with clinical repercussions related to the loss or gain of the function of the gene. In evaluating the SNP alterations individually, the results suggest that: SNPs 1,4,14, and 15 are loss of function variants; SNPs 5 and 10 are described as loss of function variants; however, they have no influence on our study population; SNPs 11 and 13 are loss of function variants and not gain of function function as is described in the literature; and SNP 12 was associated with a loss of function in our population. In conclusion, we showed that the functional polymorphisms in P2X7 are associated with Bone Mineral Density and the risk of ankle fractures. As limitations to our study, we can point out the fact that we focused mainly on nonsynonymous polymorphisms, which do not cover all the genetic variations in P2X7, and the small number of participants when compared to the world literature. On the other hand, a strength of our study is that it was the first to assess P2X7 in the Brazilian population, which is quite heterogeneous from the genetic point of view due to our miscegenation, as compared to other studies that evaluated the population of northern Europe, which is genetically more homogeneous. In conclusion, the SNP12 polymorphism in P2X7 is associated with Bone Mineral Density and the risk of ankle fractures

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-04-07T13:15:48Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Mestrado Verônica Melo CCS.pdf: 1393412 bytes, checksum: ba56180c890511d0089ae952978dcc15 (MD5)
Made available in DSpace on 2017-04-07T13:15:48Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Mestrado Verônica Melo CCS.pdf: 1393412 bytes, checksum: ba56180c890511d0089ae952978dcc15 (MD5) Previous issue date: 2016-07-01
Introdução: o uso crônico de glicocorticoides é considerado a principal causa de osteoporose secundária e iatrogênica. Existem poucos estudos associando fraturas ao uso de glicocorticoides na faixa etária pediátrica. Eles poderiam ajudar na criação de abordagens preventivas e terapêuticas. Objetivos: avaliar se o uso de glicocorticoides, nos 12 meses precedentes, associou-se à ocorrência de fraturas em crianças e adolescentes; identificar a frequência de asma e outras doenças; comparar o perfil demográfico, o tipo de trauma, o índice de massa corpórea, a prática de exercício físico, a ingesta de leite e o tabagismo passivo domiciliar nos grupos com e sem fratura; verificar a frequência de deficiência de vitamina D. Métodos: no período de abril a outubro de 2015, um estudo tipo caso controle foi conduzido em crianças e adolescentes vitimadas por trauma, com e sem fratura, a partir da análise dos dados coletados. Resultados: foram estudados 104 pacientes, 50 com fratura e 54 com trauma, mas sem fratura. Ao todo, 80,4% eram meninos e 40,4% estavam na faixa etária de 10 a 14 anos. O uso prévio de glicocorticoides ocorreu em 15,4% do total, sem diferença estatisticamente significante entre os dois grupos. Entre 39 pacientes com fratura e que dosaram a vitamina D, 47,2% tinham níveis séricos < 30ng/ml. A prática de exercício físico associou-se a um aumento em 2,2 vezes no risco para fratura. Conclusões: este estudo não mostrou associação entre o uso prévio de glicocorticoides e a ocorrência de fraturas em crianças e adolescentes. A faixa etária de 10 a 14 anos, o trauma grave e o exercício físico associaram-se com um maior risco para fraturas. Cerca de metade de uma amostra dos pacientes com fratura apresentou níveis insuficientes/deficientes de vitamina D, mesmo em região tropical.
Introduction: Osteoporosis is not exclusive to older adults and manifests by fractures. Chronic glucocorticoid use is considered the main cause of secondary and iatrogenic osteoporosis. Few studies have related fractures to the use of glucocorticoids in children and adolescents. Such studies could be useful for the development of preventive and therapeutic strategies. Objectives: To assess whether glucocorticoid use in the past 12 months is associated with the occurrence of fractures in children and adolescents; to identify the frequency of asthma and other diseases; and to compare the demographic profile, type of trauma, body mass index, physical activity, milk intake, and household exposure to cigarette smoke of groups with and without fractures; to verify the frequency of vitamin D insufficiency/deficiency. Methods: A case-control study, conducted from April to October 2015, analyzed the data of trauma children and adolescents with and without fractures. Results: A total of 104 trauma patients were studied, 50 with and 54 without fractures. In all, 80.4% were males, and 40.4% were aged 10 to 14 years. Previous glucocorticoid use occurred in 15.4% of the sample, without significant difference between the groups. Of the 39 fracture patients with measured serum vitamin D levels, 47.2% had levels < 30ng/ml. Physical activity was associated with a 2.2-fold risk of fractures, but without significance in multivariate analysis. Conclusions: This study did not find an association between previous glucocorticoid use and the occurrence of fractures in children and adolescents. In 10- to 14-year-olds, severe trauma and physical activity were associated with higher risk of fractures. About half the fracture sample had insufficient/deficient vitamin D levels, despite residing in a tropical region.

Introdução: A osteoporose (OP) é doença caracterizada pela fragilidade do osso e, consequentemente, pelo incremento do risco de fraturas. É considerada problema de saúde pública na maioria dos países. Evidências epidemiológicas apontam associação entre variáveis sociodemográficas, variáveis de estilo de vida (como a ingestão de alimentos e de bebidas alcoólicas e hábito de fumar), e indicadores antropométricos (como índice de massa corporal -IMC-) e risco de OP e fraturas osteoporóticas. Objetivo: Estimar a incidência de OP e a prevalência de fraturas referidas, em idosos domiciliados no Município de São Paulo e verificar associação com variáveis sociodemográficas, de estilo de vida, e IMC. Método: analisaram-se dados do Estudo SABE (Saúde, Bem-estar e Envelhecimento) 2000 - 2006, o qual é estudo epidemiológico, longitudinal, de base domiciliar, cuja amostra inicial foi composta por 2143 idosos (≥60 anos), de ambos os sexos, residentes habituais de domicílios urbanos no Município de São Paulo, e selecionados por amostragem probabilística, sendo que 829 idosos (39%) constituíram a amostra de estudo, em 2000, para análise da incidência de OP referida, em 2006, e 1072 idosos (50%) foi a amostra de estudo para análise de prevalência de fraturas após 60 anos referidas, em 2006. Investigou-se a associação entre variáveis sociodemográficas (sexo, grupo etário, vida no campo por 5 anos ou mais durante a infância ou adolescência, escolaridade e etnia), de estilo de vida (ingestão referida de leite e produtos lácteos, ovos e leguminosas, carnes, peixes e aves, frutas e verduras, frequência de ingestão de bebidas alcoólicas, e hábito de fumar); e variável antropométrica (IMC), com relação à referência de OP e fraturas após 60 anos, em 2006. Para verificar associação entre as variáveis categóricas e o desfecho, utilizou-se o teste de Rao & Scott (p<0,05) e a análise de regressão logística univariada (IC95%).O programa Stata, versão 10.1 foi usado para realizar os cálculos estatísticos. Resultados: Houve 114 casos novos de OP referida em 2006, sendo que o coeficiente de incidência (CI) de OP referida foi estimado em 13,93/1000 pessoas-ano (IC95%=11,60 16,87). O CI de OP referida em mulheres foi 22,95/1000 pessoas-ano (IC95%: 19,08 27,87), e 3,34/1000 pessoas-ano (IC95%: 1,85 6,73), em homens.A prevalência de fraturas após os 60 anos referidas foi 17,16%. Sexo feminino (OR= 7,69; p=0,000) e ingestão referida de bebidas alcoólicas < 4 vezes/semana (OR= 2,26; p=0,019), foram fatores de risco para referência de OP. Sexo feminino (OR=2,38;p=0,000), idade avançada (≥75 anos)(OR=1,72; p=0,012), ingestão referida de bebidas alcoólicas < 4 vezes/semana (OR=2,45; p=0,016), referência de OP em 2000 (OR=1,75; p=0,048), e referência de OP em 2006 (OR=2,29; p=0,000), foram fatores de risco para referência de fraturas após 60 anos. Conclusões: sexo feminino, idade avançada foram fatores de risco para OP e fraturas após os 60 anos. Dentre as variáveis modificáveis, a ingestão de bebida alcoólica com frequência ≥ 4 vezes/semana, esteve negativamente associado à referência de OP e fraturas após 60 anos.
Introduction: Osteoporosis (OP) is a disease characterized by bone fragility and increased risk of fractures. It is considered a public health problem worldwide. Epidemiological studies have found association between sociodemographic, lifestyle and anthropometrical variables and increased risk of OP and osteoporotic fractures. Objetive: To estimate incidence of self-reported OP, in 2006, and prevalence of fractures after the age of 60 year-old, on a sample of elderly individuals from the Município de São Paulo, and verify association between selected variables and outcome. Method: based on data from the SABE Study (health, well-being and aging) 2000 - 2006, which is an epidemiological prospective study of a probabilistic household sample of elderly population ((≥ 66 y), of both sexes, from São Paulo City, Brazil. Association between sociodemographic (sex, age, life in rural area for 5 year or more during childhood or adolescence, schooling, and race) lifestyle (reported food intake (milk and dairy products, eggs and legumes, meat, fish and poultry, fruit and vegetables), reported alcoholic beverages intake) and smoking habit; and anthropometrics\' variables, such as body mass index (BMI) and self-reported OP and fractures after the age of 60 year-old, in 2006. Rao & Scott Test was used to verify association between the categorical variables and outcome (p<0,05) as well as simple logistic regression (CI95%). Stata software, version 10.1, was used for statistical calculation. Results: There were 114 new cases of self-reported OP in 2006, and an incidence rate of 13,93/1000 persons-year (IC95%=11,60 - 16,87). In women the incidence rate was 22,95/1000 persons-year (CI95%: 19,08 - 27,87), and in men it was 3,34/1000 persons-year (IC95%: 1,85 - 6,73). Prevalence of self reported fractures after de age of 60 y was estimated in 17,16%. Female sex (OR= 7,69; p=0,000) and frequency of reported alcoholic beverages intake < 4 times/week (OR= 2,26; p=0,019), were risk factors for self-reported OP. Female sex (OR=2,38;p=0,000), advanced age (≥75 y) (OR=1,72; p=0,012), frequency of reported alcoholic beverages intake < 4 times/week (OR=2,45; p=0,016), self-reported OP in 2000 (OR=1,75; p=0,048), and self-reported OP in 2006 (OR=2,29; p=0,000), were risk factors for reporting fractures after the age of 60 years-old Conclusions: female sex, advanced age, were risk factors for reported OP and fractures after 60 y. Among modifiable variables, intake of alcoholic beverages as often as > 4 times/week was negatively associated with reported OP and fractures after the age of 60 y.

Background: The global burden of osteoporosis includes considerable numbers of fractures, morbidity, mortality and expenses, due mainly to vertebral, hip and forearm fractures. Underdiagnosis and undertreatment are common. Several studies have shown decreased health-related quality of life (HRQOL) after osteoporotic fracture, but there is a lack of data from long-term follow-up studies, particularly regarding vertebral fractures, which are often overlooked despite patients reporting symptoms. Aim: The overall aim of this thesis was to evaluate the usefulness of a recent low-energy fracture as index event in a case-finding strategy for osteoporosis and to describe and analyse long-term HRQOL in postmenopausal women with osteoporotic fracture. The specific aims were to describe bone mineral density and risk factors in women 55-75 years of age with a recent low-energy fracture (I), estimate the impact of osteoporotic fractures on HRQOL in women three months and two years after a forearm, proximal humerus, vertebral or hip fracture (II), investigate the changes and long-term impact of vertebral or hip fracture on HRQOL in women prospectively between two and seven years after the inclusion fracture (III), and describe how HRQOL and daily life had been affected in women with vertebral fracture several years after diagnosis (IV). Design and methods: Data were collected from southern Sweden between 1998 and 2008. A total of 303 women were included in Study I, and this group served as the basis for Studies II (n=303), III (n=67), and IV (n=10). A cross-sectional observational, case-control design (I), and a prospective longitudinal observational design (II-III) were used. In Study IV a qualitative inductive approach with interviews was used and data were analysed using a qualitative conventional content analysis. Results: The type of recent fracture and number of previous fractures are important information for finding the most osteoporotic women in terms of severity (I). Hip and vertebral fractures in particular have a significantly larger impact on HRQOL evaluated using the SF-36 than do humerus and forearm fractures, both during the three months after fracture and two years later, compared between the different fracture groups and the reference population (II). Women who had a vertebral fracture as inclusion fracture had remaining pronounced reduction of HRQOL at seven years. At the mean age of 75.5 years (±4.6 SD), the prevalence of vertebral fracture suggests more negative long-term impact on HRQOL, more severe osteoporosis and a poorer prognosis than a hip fracture does, and this effect may have been underestimated in the past (III). Study IV demonstrates that the women’s HRQOL and daily life have been strongly affected by the long-term impact of the vertebral fracture several years after diagnosis. The women strive to maintain their independence by trying to manage different types of symptoms and consequences in different ways. Conclusions and implications: Type and number of fractures should be taken into account in the case-finding strategy for osteoporosis in postmenopausal women between 55 and 75 years of age. The long-term reduction of HRQOL in postmenopausal women (age span 55-75 yr) with vertebral fracture emerged clearly, compared to women with other types of osteoporotic fractures and references in this thesis. The results ought to be taken into consideration when developing guidelines for more effective fracture prevention and treatment, including non-pharmacological intervention for women with osteoporotic fractures, with highest priority placed on vertebral fractures and multiple fractures, to increase or maintain HRQOL.

Abstract Genetic factors and their resulting phenotypes were evaluated in three different bone disorders: osteogenesis imperfecta (OI), juvenile idiopathic osteoporosis (JIO), and stress fractures. The spectrum of the OI phenotypes caused by mutations in the COL1A1 and COL1A2 genes is well defined, but the mechanisms by which the variations affect the hearing phenotype are not well-known. A total of 54 Finnish OI patients with previously diagnosed hearing loss, or aged 35 or more years, were analyzed here for mutations in COL1A1, or COL1A2. Altogether, 49 mutations were identified, of which 41 were novel. No correlation was observed between the mutated gene, or the mutation type, and the hearing pattern. This indicates that the basis of hearing loss in OI is complex, and is a result of multifactorial, still unknown genetic effects, or of variable expressions of the COL1A1 and COL1A2 genes. JIO presents peri-pubertally as an acute symptomatic osteoporosis (bone pain and fractures) in otherwise healthy children, and no underlying cause has yet been identified for this disorder. Here, the analysis of the low-density lipoprotein receptor-related protein 5 gene (LRP5) in 20 patients with JIO revealed two missense mutations (A29T and R1036Q) and one frameshift mutation (C913fs) in 3 of the patients. The LRP5 gene has recently been shown to be also involved in osteoporosis-pseudoglioma syndrome and a high-bone-mass phenotype. Stress fractures are a significant problem among athletes and soldiers. Genetic factors may increase the fracture risk, but no susceptibility genes have yet been identified. Seven genes involved in bone metabolism, or pathology, were studied in terms of their roles in stress fracture. No disease-causing, or predisposing variations were found in the candidate gene, or association analyses, but a highly significant association was found between the phenotype and a vitamin D receptor (VDR) haplotype, TGT, which is composed of three polymorphic sites, FokI, BsmI and TaqI. We showed that femoral neck stress fractures are associated with a certain VDR haplotype, accounting for a five-fold increase in the risk of developing stress fractures, with an associated attributable risk of 12%. The results of this study show that genetic factors play a role in different pathological bone phenotypes. These findings provide new information on the pathogenesis of the disorders and for the development of genetic testing and targeted treatment for the disorders.

Orientador: Djalma de Carvalho Moreira Filho
Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-16T10:58:46Z (GMT). No. of bitstreams: 1 Vidal_EdisonIglesiasdeOliveira_D.pdf: 5523772 bytes, checksum: 95d09fb9d160d1f4bfcc3cfe1b5a30d9 (MD5) Previous issue date: 2010
Resumo: As fraturas do fêmur proximal (FFP) correspondem a um importante problema de saúde pública em todo o mundo. Dentre todas as fraturas associadas à osteoporose são consideradas como as mais graves e correlacionam-se com os maiores índices de morbimortalidade, dependência funcional e custos para os indivíduos e os sistemas de saúde. O maior crescimento em sua incidência nos próximos anos é esperado nos países em desenvolvimento, todavia, estes também são os locais onde é maior a carência por dados acerca da epidemiologia dos pacientes acometidos por estas fraturas. A presente pesquisa teve como objetivo analisar alguns aspectos desta epidemiologia tanto no âmbito nacional como internacional. Como resultado foram confeccionados três artigos abordando esta temática. O primeiro artigo avaliou, a partir de uma base de dados de todas as hospitalizações por FFP na província de Quebec, no Canadá, a hipótese da equivalência do intervalo de tempo entre a fratura e a cirurgia e o intervalo entre a hospitalização e a cirurgia, enquanto preditores da ocorrência de óbito intra-hospitalar. Após controle para a presença de outras variáveis, nenhum dos intervalos mostrou associar-se com a mortalidade intra-hospitalar. Concluiu-se que, ao menos na medida em que a diferença entre os intervalos sejam pequenas como no caso observado, os mesmos podem ser utilizados de modo intercambiável sem comprometer a interpretação da associação entre o timing cirúrgico e a mortalidade intra-hospitalar, tal como pressuposto em diversos estudos prévios da literatura internacional. O segundo artigo buscou caracterizar o perfil clínico de idosos brasileiros hospitalizados em função de uma FFP, bem como os padrões de tratamento adotados, as complicações intra-hospitalares e a mortalidade ao longo de um ano. Dentre outros resultados de interesse, observou-se uma taxa de mortalidade em um ano de 13,4% (IC95%: 10,1 - 17,5%) e intervalos bastante elevados tanto entre a fratura e a hospitalização (média de 3,6 dias) como entre a internação e a cirurgia (média de 12,8 dias). O terceiro artigo procurou avaliar dentro do contexto brasileiro a associação entre o intervalo de tempo da fratura à cirurgia e a sobrevida dos idosos acomeditos por uma FFP. Após ajuste para variáveis de confundimento observou-se uma associação entre uma maior demora para a internação hospitalar e o óbito (HR: 1,08 , IC95%: 1,04 - 1,12, P < 0,001). Discute-se a questão das FFP enquanto objeto epidemiológico privilegiado, inclusive como um possível evento sentinela a ser monitorado no âmbito da saúde do idoso tanto no plano nacional como internacional.
Abstract: Hip Fractures (HF) represent the most severe of all osteoporotic fractures and remain an important cause of mortality, morbidity, dependency and costs for older adults and healthcare systems worldwide. Even though the greatest increase regarding the incidence of HF is expected to occur in the developing countries of the World, those are also the regions from where less information is available regarding the epidemiology of those fractures. The present research aimed to analyze selected aspects of the epidemiology of those fractures both in Brazil and internationally. Three manuscripts were produced as a direct result of this investigation. The first manuscript assessed the widely adopted assumption of interchangeability between the gap from hospital admission to surgical HF repair and the actual gap from fracture to surgery as predictors of in-hospital mortality among HF patients. A database encompassing all HF hospital admissions in Quebec, Canada, was the primary source of data for the analyses undertaken in this study. After statistical adjustment for the presence of other covariates neither of the time intervals to surgery was a significant predictor of in hospital mortality. As a conclusion, at least to the extent of the small differences observed between both gaps, they might be used interchangeably without compromising the interpretation of the relationship between surgical timing and in-hospital mortality, as assumed by previous studies. The second manuscript aimed to describe the clinical profile, treatment patterns, in hospital complications and one-year mortality of elderly Brazilians with an incident HF. Among other findings 13.4% (95%CI: 10.1% - 17.5%) of patients died during the first year and large gaps from fracture to hospital admission (mean 3.6 days) and from hospital admission to surgery (mean 12.8 days) were noted. The third manuscript examined in the context of a developing country the association between surgical timing and the survival of older adults after a HF. After adjusting for the presence of other covariates a small association between delayed hospital admission and reduced survival (HR: 1.08, 95% CI: 1.04 - 1.12) was observed. The point is made that HF should be considered a privileged epidemiological object, which might be used strategically as a sentinel event to be monitored both locally and internationally as a marker of the quality of health care to the elderly.
Doutorado
Epidemiologia
Doutor em Saude Coletiva

O envelhecimento normal é um processo contínuo, que desencadeia alterações psicossociais e biológicas, não afetadas por patologias. Estas mudanças podem desencadear perdas de ordem neuromuscular e óssea, influenciando o aparelho locomotor dos idosos. A osteoporose é uma doença que afeta sistêmica e progressivamente o esqueleto sendo as fraturas sua principal consequência, especialmente na coluna vertebral. A identificação destas fraturas pode ser realizada através da morfometria vertebral, analisadas através de raios-X (MRX) ou absorciometria de raios-X (MXA), que consideram morfologia da vértebra através da comparação da altura de seus contornos em 6 pontos diferentes. As mulheres, sobretudo na pós-menopausa, estão mais susceptíveis a fraturas. A prescrição de exercício, não deve somente agregar benefícios físicos, mas também deve considerar a predisposição ao surgimento de novos agravos, como as fraturas. Os exercícios de alta intensidade na água podem funcionar como um recurso seguro para uma população normalmente fragilizada pela idade. Assim, o objetivo da pesquisa foi verificar se a sobrecarga mecânica causada por um programa de exercícios aquáticos de alta intensidade é segura para a morfologia da coluna vertebral de mulheres na pós-menopausa. Trata-se de um estudo prospectivo e controlado onde foram analisadas 108 mulheres sedentárias na pós-menopausa, distribuídas em um grupo com fratura (n=20) e outro sem fratura (n=88). O grupo foi classificado em controle (GC) (n = 44) composto por idosas sedentárias e intervenção (GI) (n = 64), formado por aquelas que participaram do protocolo de hidroginástica. Todas as participantes receberam suplementação oral com 500 mg de cálcio e 1000 UI de Vitamina D3 e foram submetidas a uma avaliação inicial e após 24 semanas de intervenção com um programa de hidroginástica. Foram avaliados os dados antropométricos, informações sobre parâmetros de dor, testes aplicados para variáveis neuromusculares e realização de densitometria óssea seguida de morfometria para identificação de fraturas. Os achados apontaram que 18,51% das mulheres presentaram fraturas, predominantemente localizadas na coluna torácica a região anterior da vértebra. Observou-se mudanças significativas para força, flexibilidade e dimuição do número de quedas nos grupos com e sem fratura (p<0,05). A presença de fraturas esteve associada à idade, Índice de Massa Corpórea (IMC) e Conteúdo Mineral Ósseo (CMO) do trocânter do fêmur (p<0,0001). O desempenho nas variáveis estudadas do GI é superior ao GC, mesmo nas mulheres fraturadas inseridas neste grupo. O protocolo utilizado foi seguro para as mulheres pós menopausadas
Normal aging is a continuous process that results in biological and psychosocial changes, unaffected by pathologies. These changes can lead to a loss in neuromuscular and skeletal order, impacting the locomotors system in the elderly. Osteoporosis is a systemic disease that progressively affects the skeleton structure where the fractures its main consequence, mainly in the spine. The gauged of these fractures can be assessed by vertebral morphometry, by using X-ray (MRX) or X-ray absorptiometry (MXA), which consider the vertebra morphology trough comparison between the heights of its contours in 6 different points. The women, especially postmenopausal, are more susceptible to fractures. The exercise prescription should not just add physical benefits, but also consider the predisposition to the rise of new injuries, such as fractures. The high-intensity exercise in the water can act as a safety feature for a population usually weakened by age. The goal of this research was the investigation if a mechanical overload caused by a program of high-intensity water exercise is safe for the spine morphology in postmenopausal women. A prospective and controlled study was made where 108 postmenopausal sedentary women were distributed in a fracture group (n = 20) and one without fracture (n = 88). The group was distributed in control (CG) (n = 44) composed by sedentary elderly and intervention (GI) (n = 64), formed by those who participated in the protocol for water exercises. All participants received oral supplementation with 500 mg calcium and 1000 IU of Vitamin D3 and were submitted to an initial assessment and 24 weeks after intervention of water exercises. Were evaluated anthropometric data, information on ethnicity, pain parameters, neuromuscular tests applied to variables and performing bone densitometry followed by morphometry to identify fractures. The findings showed that 18.51% of the women present fracture, predominantly located in the anterior thoracic spine. Were observed significant changes for strength, flexibility and a reduction of fall´s in a group with and without fracture (p <0.05). The presence of fractures was associated with age, body mass index (BMI) and bone mineral content (BMC) of the femoral trochanter (p <0.0001). The performance variables have best scores in GI than GC, even in fractured women included in this group. The protocol used was safe for postmenopausal women

Abstract Osteoporotic hip fractures are associated with high mortality and morbidity rates as well as significant costs. Low-frequency (LF) axial transmission ultrasound is a promising modality for assessing mineral density and geometrical properties. Thus, it may yield additional information on the risk of osteoporotic fractures. This study aimed to evaluate the ability of LF ultrasound to assess osteoporotic status and the risk of fracture in postmenopausal women. Also, lifestyle-related risk factors of hip fractures and the additional discrimination value of combining lifestyle-related risk factors and LF ultrasound velocity were assessed. Two study populations were used. The first consisted of 1,222 older women. Lifestyle-related risk factors and mobility were assessed at baseline. The women were followed for 13 years and the fractures that occurred were recorded. A subgroup of the women was later measured with LF ultrasound and dual-energy x-ray absorptiometry (DXA). The other study population included 95 postmenopausal women whose fracture history was gathered and bone status assessed with LF ultrasound, DXA and peripheral quantitative computed tomography (pQCT). Low body mass and impaired mobility predicted hip fractures. In addition, the risk of cervical hip fracture was increased by low physical activity and decreased by moderate coffee consumption and hypertension. Smoking and old age increased the risk of trochanteric hip fracture. The LF ultrasound velocity reflected to some degree the geometry and bone mineral density of the proximal femur. Decreased low-frequency ultrasound velocity was a significant risk factor of hip fracture even when combined with lifestyle-related risk factors. The LF ultrasound method showed similar fracture discrimination ability compared to DXA and pQCT, especially on the radius. In conclusion, the LF ultrasound method showed promising results in bone characterization and fracture discrimination. Further prospective studies with larger population are needed to confirm the combined effect of clinical risk factors and LF ultrasound
Tiivistelmä Osteoporoottisiin lonkkamurtumiin liittyy korkean sairastavuuden ja kuolleisuuden lisäksi huomattavat taloudelliset kustannukset. Tässä työssä tutkittiin matalataajuisen ultraäänitekniikan soveltuvuutta osteoporoosin ja murtumariskin arviointiin. Matalataajuista luun pituusakselin suuntaista ultraäänitekniikkaa voidaan käyttää luun mineraalitiheyden ja rakenteen tutkimiseen. Lisäksi tutkittiin elintapoihin liittyviä lonkkamurtuman riskitekijöitä sekä näiden yhdistämistä ultraäänimittaustulosten kanssa riskimalliin. Tutkimuksessa käytettiin kahta tutkimuspopulaatiota. Ensimmäisen muodosti 1222 ikääntynyttä naista, joiden elintavat ja liikuntakyky kartoitettiin tutkimuksen alussa. Kolmentoista vuoden seuranta-ajan aikana tapahtuneet murtumat kerättiin potilasarkistoista. Osa naisista osallistui matalataajuisella aksiaalisuuntaisella ultraäänellä tehtyyn mittaukseen ja kaksienergiseen röntgentutkimukseen (DXA). Toinen tutkimuspopulaatio koostui 95 postmenopausaalisesta naisesta. Naisten murtumahistoria kerättiin ja heille tehtiin matalataajuinen ultraäänimittaus sekä DXA- ja perifeerinen tietokonetomografiatutkimus (pQCT). Alhainen painoindeksi ja heikentynyt liikuntakyky lisäsivät lonkkamurtuman riskiä. Vähäinen fyysinen aktiivisuus lisäsi ja kohtalainen kahvinjuonti ja verenpainetauti alensivat reisiluun kaulan murtumariskiä. Tupakointi ja korkea ikä kasvattivat sarvennoisen alueen lonkkamurtuman riskiä. Matalataajuisen ultraäänen nopeus oli yhteydessä reisiluun yläosan geometriaan ja mineraalitiheyteen. Alhainen ultraäänen nopeus oli merkittävä lonkkamurtuman riskitekijä sekä yksin että yhdistettynä elintapamuuttujiin. Lisäksi ultraäänimenetelmä saavutti röntgenmenetelmiin (DXA ja pQCT) verrattavan erottelukyvyn murtumapotilaiden ja kontrollihenkilöiden välillä. Tutkittu ultraäänimenetelmä osoittautui lupaavaksi työkaluksi luun karakterisoinnissa ja murtumariskin arvioinnissa. Laajempia seurantatutkimuksia tulosten vahvistamiseksi tarvitaan erityisesti elintapoihin liittyvien riskitekijöiden ja ultraäänen yhdistämisen osalta

Hip fracture is the most common reason for admission to an orthopaedic trauma word. It is usually a 'Fragility' fracture caused by a fall affecting an older person with osteoporosis or osteopenia (a condition in which bones lose calcium and become thinner, but not as much as in osteoporosis). The National Hip Fracture Database worldwide reports the average age of a person with hip fracture is 84 years for men and 83 years for women, 76% of fracture occurs in women. By 2050, the worldwide incidence of hip fracture in men is projected to increase by 24% in women and 31% in men. Hip fractures due to sideways falls are a worldwide health problem, especially amongst elderly people. The experienced force to the proximal femur during a fall leading to hip fracture is significantly dependent on density, thickness and stiffness of the body during impact. The process of fracture and healing can only be understood in terms of structure and composition of the bone and also its mechanical properties. Bone fracture analysis investigates to predict various failure mechanisms under different loading conditions. In an effort to improve and assist scientists and researchers to predict the impact damage response of bone structures and estimate femoral fracture load in vitro, an accurate explicit finite element (14E) method has been investigated in this study. In the first part, the main goal is to create a 3D reconstruction and registration of semi-transparent Computed Tomography (CT) scan image data using SIMPLEWARE software. In the second part, effect of cortical thickness and impact velocity on the energy absorption of hip during a fall has been investigated on a 3D model. Additionally composite femora were mechanically tested to failure and regression analyses between measured fracture load and FE-predicted fracture load were performed. The results indicate that this sophisticated technique, which is still early in its development, can achieve precision comparable to that of densitometry and can predict femoral fracture load to within 18% with 95% confidence.

Thesis (M.S.)--West Virginia University, 2003.
Title from document title page. Document formatted into pages; contains x, 100 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 91-96).

Orientador: Lucia Helena Simões da Costa Paiva
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-11T15:10:52Z (GMT). No. of bitstreams: 1 Ferreira_NevilledeOliveira_M.pdf: 789783 bytes, checksum: 5dfd61c25cd1bdee8f3b7700bbb2088e (MD5) Previous issue date: 2008
Resumo: OBJETIVO: avaliar a qualidade de vida (QV) e fatores associados em mulheres com osteoporose pós-menopausa correlacionado QUALEFFO 41 com o SF-36. MÉTODOS: realizou-se um estudo de corte transversal com 220 mulheres pósmenopausa (idade entre 55-80 anos), sendo 110 com osteoporose e 110 sem osteoporose, pareadas por idade (± 3anos). Todas foram entrevistas para avaliação da QV realizada através de dois questionários: Quality of Life Questionary of European Foudation for Osteoporosis 41 (QUALEFFO 41) e o Short Form Health Survey 36 (SF-36). Para análise dos dados foi considerado um nível de significância de 5% (p<0,05). RESULTADOS: as características clínicas entre os grupos foram similares, com diferença estatisticamente significativa apenas em relação ao Índice de Massa Corpórea (IMC), raça, escolaridade, idade da menopausa e uso de Terapia Hormonal (TH) (p<0.001). Mulheres com osteoporose apresentaram pior QV tanto no QUALEFFO 41 quanto SF-36, para todos os domínios estudados sendo os dados ajustados para IMC, raça, escolaridade e uso de TH (p<0.001). Houve correlação significativa entre todos os domínios do QUALEFFO 41 com seus correspondentes do SF-36 (p<0.001) Os únicos fatores relacionados à pior QV foram IMC>25 e sedentarismo, já o trabalho remunerado esteve associado à melhor QV (IC=95%). CONCLUSÃO: Mulheres com osteoporose apresentam comprometimento da qualidade de vida particularmente nos aspectos físicos e psico-sociais. Os fatores associados à QV foram a obesidade, o sedentarismo e o trabalho remunerado. Palavras-chave: osteoporose, qualidade de vida, fratura vertebral, QUALEFFO 41, SF-36
Abstract: OBJECTIVE: To evaluate quality of life (QoL) and associated factors in women with postmenopausal osteoporosis, correlating QUALEFFO 41 with SF-36. METHODS: A cross-sectional study was conducted in 220 postmenopausal women (ages ranging from 55-80 years). Of the total number, 110 women had osteoporosis and 110 women did not have osteoporosis and these women were paired by age (± 3 years). Two questionnaires were administered to all subjects for evaluation of QoL: the Quality of Life Questionnaire of the European Foundation for Osteoporosis 41 (QUALEFFO 41) and the Short-Form Health Survey 36 (SF-36). For data analysis, a significance level of 5% was set (p<0.05). RESULTS: Clinical characteristics between the groups were similar, with statistically significant differences only in Body Mass Index (BMI), race, school education, age at menopause and use of Hormone Therapy (HT) (p<0.001). Women with osteoporosis had a worse QoL both in the QUALEFFO 41 and in the SF-36, in all domains studied. Data was adjusted for BMI, race, school education and use of HT (p<0.001). There was a significant correlation between all domains in the QUALEFFO 41 questionnaire and their corresponding domains in the SF-36 (p<0.001). The only factors related to worse QoL were BMI>25 and sedentary lifestyle. In contrast, paid work was associated with a better QoL (CI=95%). CONCLUSION: Women with osteoporosis had an impaired quality of life, especially relating to the physical, psychological and social aspects. The factors associated with QoL were obesity, sedentary lifestyle and paid work. Keywords: osteoporosis, quality of life, vertebral fracture, QUALEFFO 41, SF- 36
Mestrado
Ciencias Biomedicas
Mestre em Tocoginecologia

Osteoporosis is a condition that decreases bone density and is more commonly found in elderly women due to estrogen depletion. The decrease in bone density puts patients at risk for fragility fractures, or fractures with minimal impact, which can drastically alter patients? lives. Primary prevention of these fractures is the goal with pharmacologic therapy for osteopenia or osteoporosis. There are many treatment options for osteoporosis and most are considered cost effective for patients with high fracture risk due to decreased bone density. Treatment decisions for osteopenia or osteoporosis are now based upon a fracture risk assessment tool in addition to T-score values. Studies have demonstrated that adherence to pharmacologic therapy to decrease fracture risk and maintain bone density is an issue with the majority of patients. Most patients are not staying on treatment for greater than one year for a variety of reasons. A practice improvement project was conducted at an internal medicine private practice clinic that serves 10,000 patients in a Midwestern community. The project included retrospective chart reviews and key informant interviews in order to gain expanded knowledge of the issue and provide recommendations for improvement. Results showed inconsistent documentation of patient treatment preferences and provider treatment decisions. Additional areas for improvement included patient and provider follow up of treatment decisions as well as patient education regarding the disease process and benefits of treatment. Results and recommendations for improvement were disseminated to providers at the clinic with feedback solicited. An electronic medical record change was implemented in order to improve documentation of treatment decisions regarding elevated fracture risk. The results of the project may not be transferrable due to small sample size and area of focus at one Midwest clinic. However, themes regarding clinical decision-making and documentation of osteoporosis treatment emerged that likely exist at other primary care clinics. Further research is needed in order to evaluate effectiveness of electronic medical record intervention at the clinic. Other opportunities for further research involve expanding the topic to larger healthcare organizations and other areas of the country for comparison.

Vertebral fragility fractures are common, affecting approximately 50% of all postmenopausal women and 33% of men over the age of 50, and are the most common type of fracture seen in osteoporosis. The management of vertebral fragility fractures in the acute care setting is lacking in standardization, in the use of evidence-based practice, and in addressing the underlying cause of osteoporosis. The purpose of this project was to develop an evidence-based protocol to standardize the care of the vertebral fragility fracture in the acute care setting. This protocol included patient education, fall risk assessment, screening for osteoporosis, and follow up with an osteoporosis clinic for comprehensive management once discharged. This project used the Donabedian model to provide a conceptual framework for evaluating the structure, process, and outcomes related to the practice problem. This quantitative study involved 10 participants that were selected using purposive sampling and used process control charting to show compliance with elements of the guideline, and descriptive data to depict process change. Guideline compliance was measured over an 8-week period and indicated successful implementation of fall risk assessment with a 100% compliance rate and osteoporosis screening with an 80% compliance rate. Compliance with fracture education and securement of follow up were difficult to ascertain in the 8-week period and non-compliance evident. In conclusion, two elements of the guideline showed to be an unstable process and further work is necessary to improve. Positive social change may result from empowering nurses by education and giving them autonomy to use evidence-based practice to decrease the risk for secondary vertebral fragility fractures.

Avaliar as propriedades mecânicas em dois sistemas de osteossíntese com o emprego de placa volar de rádio distal, alterando-se o tipo de parafuso utilizado quais sejam: bloqueados ou corticais, na fileira distal da placa bem como a colocação ou não de enxerto ósseo em modelos ósseos Sawbone(TM). Trata-se de um estudo experimental de fraturas do rádio distal extra articular, consideradas instáveis, com dois fragmentos e com uma cunha dorsal de 11 mm (classificação AO 23 A3) e também com modelo de osteotomia de cunha aberta, frequentemente empregado por cirurgiões ortopédicos, na prática clínica. Foram usados 10 (dez) ossos rádios Sawbone(TM) esquerdos (Código: 3407), validados para estudo biomecânico, os quais foram divididos em dois grupos de cinco ossos cada. Os grupos foram submetidos a dois sistemas de osteossíntese: sistema de fixação 1, placa volar de ângulo variável esquerda VA-LCP, dupla coluna, seis/três furos, com quatro parafusos bloqueados distais, dois parafusos bloqueados proximais e mais um parafuso cortical proximal e o sistema de fixação 2, utilizou a mesma placa volar de rádio, porém apenas trocou na fileira distal os quatros parafusos corticais. Os modelos foram submetidos a testes mecânicos de flexão dorsal de 30 N e compressão axial de 250 N para avaliar a deflexão e a rigidez dos sistemas, alternando a colocação do enxerto ósseo. A seguir, houve o ensaio de carregamento cíclico de compressão de 250 N por 1000 HZ, simulando-se um pós-operatório de 6 semanas. Na segunda parte do estudo, foram realizados os mesmos testes de compressão axial e flexão dorsal, usando as mesmas forças de carregamento empregadas na primeira fase dos ensaios mecânicos, para avaliar as possíveis alterações na deflexão e rigidez. Para se comparar as medidas aferidas entre os testes de flexão dorsal e compressão axial antes e depois do carregamento cíclico foi empregado o teste de U de Mann-Whitney, considerando-se um nível de significância de 5%. Ao analisar os resultados obtidos, o sistema de fixação com parafuso cortical com enxerto (CC) se mostrou mais rigído, tanto na deflexão quanto na compressão ao ser comparado com os demais sistemas de fixação, principalmente com o bloqueado sem enxerto (BS). Quanto a relevância clínica do estudo placas volar de rádio distal são comumente usadas nos tratamentos das fraturas do rádio distal, porém a configuração ideal dos parafusos distais não foi determinada. O sistema de fixação com quatro parafusos corticais com enxerto ósseo do ponto de vista biomecânico in vitro, os resultados se mostraram bastante confiáveis como uma proposta de tratamento.
Evaluating the biomechanical properties in two osteosynthesis systems using a volar distal radius plate by changing the type of screw used, whether locked or cortical, in the distal row of the plate, with or without bone grafting in Sawbone (TM) models. This is an experimental study of fractures of the extra articular distal radius, considered to be unstable, with two fragments and a dorsal wedge of 11 mm (AO 23 A3 classification), as well as the open-wedge osteotomy model frequently used by Orthopedic surgeons, in clinical practice. Ten left-hand radios bones, Sawbone (TM) (Code: 3407), validated for biomechanical studies were used. These were then divided into two groups of 5 bones each. The groups were submitted to two osteosynthesis systems: fixation system 1, VA-LCP left variable-angle volar plate, double-column, 6/3 holes, with four distal locked screws, two proximal locked screws and one proximal cortical screw. The fixation system 2 used the same volar plate, but only the four cortical screws were changed in the distal row. The models were submitted to mechanical tests of dorsal flexion of 30 N and axial compression of 250 N to evaluate the deflection and stiffness of the systems, changing the placement of the bone graft. Next, there was the cyclic loading test of 250 N per 1000 HZ, simulating a 6-week post-op. In the second part of the study, the same tests of axial compression and dorsal flexion were performed, using the same loading forces used in the first phase of the mechanical tests to evaluate the possible changes in deflection and stiffness. In order to compare the results between the dorsal flexion tests and axial compression before and after the cyclic loading, the Mann-Whitney U test was used, considering a level of significance of 5%. When analyzing the results obtained, the cortical screw fixation system with graft was shown to be more rigid, both in deflection and in compression when compared to the other fixation systems, especially with the locked system without graft. Regarding the clinical relevance of the study, the volar distal radius plate is commonly used in the treatments of distal radius fractures, however the ideal configuration of the distal screws has not yet been determined. The results of the fixation system with four cortical screws with bone graft, from a biomechanical point of view in vitro, proved to be a reliable form of treatment.

Thesis (M.S.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Background: In 2001 an assessment tool for predicting fracture risk in postmenopausal women was developed. An index based on a small number of risk factors that are easily assessed was developed called the Fracture Index. The value of this index ranges from 0-13 with higher number associated with higher five year probability of fracture. The magnitude of the morbidity and mortality associated with osteoporosis makes it valuable for health care professionals to know if a treatment to prevent fractures is cost effective or not. Objective: To investigate at what Fracture Index value it becomes cost effective to treat postmenopausal women with alendronate to prevent hip fractures. The focus is on Icelandic women. Design: A Markov model was developed to model the disease progression for women 65 years of age to 85 years of age which is the average life expectancy for women in Iceland. Cost effectiveness of alendronate vs. no treatment was assessed by transitioning women in the model every six months between different health states. In the base-case five year treatment with alendronate was assumed. Results: At Fracture Index 1-2 the incremental cost effectiveness ratio (ICER) was 27,467,073 ISK (238,844$) which is not considered to be cost effective. At Fracture Index 3-4 the ICER was 4,349,2511SK (37,820$) which has a 59% probability of being cost effective if the per capita GOP (4,800,000 ISK) for Iceland is used as a threshold for cost effectiveness. However cost effectiveness for Fracture Index 3-4 depends largely on the assumptions made in the model, some of which are uncertain such as drug cost, drug efficacy and appropriate discount rate. Treatment with Alendronate is cost effective for Fracture Index 5 and variation in the model's assumptions does not change that result. Conclusions: The results of this study indicate that treating osteoporotic women with alendronate to prevent hip fractures becomes cost effective at Fracture Index 5 with a 1.9% five year probability of hip fracture.
2031-01-01

Introduction: An osteoporotic fracture affects every other woman and every fourth man in Sweden. To meet the needs, Örebro County implemented in 2007 a fracture liaison service(FLS) to identify, investigate and treat these patients. Aim: To evaluate the efficacy of the FLS in Örebro County by reporting the prevalence ofbone mineral density testing and anti-osteoporotic treatment initiation following a low traumafracture. Secondary aim was to evaluate adherence to treatment after 12 months. Methods: 1269 medical records were retrospectively examined for all patients, 50-85 yearsold, with a fractured wrist, upper arm, hip, pelvis or vertebra in Örebro County in 2016.Patient characteristics and continuation through the FLS was studied. Primary objectives wereall descriptive, but various subgroups were compared using chi-square and independent ttests.Limit of significance at p<0.05. Results: 738 patients were eligible for inclusion (mean age 71.00 (±9.16) years, 76.6%women). 391 (53.0%) were referred for investigation, of which 348 (89.0%) attended. 253(72.7%) of the measured patients had indication for treatment, later prescribed to 76.7% ofthese, mainly once weekly oral bisphosphonates (64.4%). Adherence after 12 months wasavailable for 176 patients, of which 119 (67.6%) were still persistent. Conclusion: The FLS in Örebro County seems to be in line with national and internationalcounterparts. Still, there is room for improvement. The major gap appears to be identificationand referral for investigation of patients at risk of osteoporosis. Once passed the identificationstep, the losses through the program are in much smaller proportions.

As the Salvadoran population's life expectancy increases, fractures among the elderly are also increasing. There is a dearth of data available on the incidence and cause of fractures in the elderly within developing countries including El Salvador. Inadequate knowledge about bone health and osteoporosis among the elderly is contributing to health issues in the aging population. The purpose of this study was to investigate incidence, knowledge, causes, and risk factors affecting elderly patients admitted for fractures at Hospital Zacamil in order to develop programs targeted to prevention. Study objectives included: 1) determine incidence, causes, and treatment of elderly fractures including hip fractures, vertebral fractures, and forearm fractures and related post-morbidity and/or mortality; 2) compare patient knowledge, cause, treatment of fractures and related post-morbidity and/or mortality among those aged 45 to 65 years with those over 65 years; 3) determine the level of knowledge and presence of risk factors for fractures and osteoporosis among patients including diet, exercise, and environmental risk factors and compare by gender. The research was approved by IRB prior to data collection. The methodology included a researcher-designed and validated survey administered to an accepting sample of 155 patients presenting with fractures to Hospital Zacamil between January 2008 and May 2008. The data were analyzed with SPSS software. Findings indicate that the incidence of fractures in the study sample and those in developed countries are similar. Knowledge and presence of risk factors are similar by age and gender within the study sample. The primary conclusion was that education is needed to prevent falls and osteoporosis. Recommendations for further research include recognition of culturally-specific factors in prevention education and further study of the methods of addressing prevention in the specified population and the outcomes of the educational intervention.
Ph. D.

Thesis (M.S.)--West Virginia University, 2001.
Title from document title page. Document formatted into pages; contains viii, 88 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 81-88).

Introduction: Currently, there is an increase in the life expectancy of the persons. It reflects the change in the epidemiological profile of the Brazilian population. Moreover, the biggest consequences faced due to this context is the increase in the prevalence of chronic comorbidities, among them, the osteoporosis. This pathology affects especially women in the post-menopause, and its main consequences are the fractures. They are responsible for an elevated morbidity and mortality that led to onerous treatments. On the other hand, nutrition represents an important role in the formation and maintenance of the bone mass. Considered now a part of the non-pharmacological treatment, a balanced alimentation, both in quality and quantity, probably will supply the necessary nutrients to maintain, at least in part, a regular bone health during the aging. Furthermore, it could be a possible protection factor for the main consequences of the osteoporosis in elderly. Objectives: to describe the alimentary consumption of calcium, phosphorus, magnesium, and proteins in women hospitalized for bone fractures in a service of Tertiary care at Rio Grande do Sul/RS. Methods: A case-control study was carried out at a university hospital. Women, 55 or older were invited to participate. Sixty-two women were recruited (42 women with fractures and 20 women without fractures). Information about clinical data and social history were recorded. An anthropometric evaluation was performed. A Questionnaire Quantitative of the Frequency of Foods (QQFA) to evaluate the ingestion of calcium, phosphorus, magnesium and proteins was applied. Results: the ingestion of calcium and magnesium was significant lower in women with fractures [446,9 mg/day vs. 689,90 mg/day and 135,49 mg/day vs.188,92 mg/day, respectively]. In the logistic regression analysis of fractures, high ingestion of calcium and magnesium were associated with a low odds of fracture. This result was adjusted for age and BMI. There were no differences in the protein and phosphorus intake between the groups. Conclusion: the studied women presented an ingestion of calcium and magnesium well below the current recommendations for sex and age group. Regarding the factors associated with the fracture, dietetic ingestion of calcium and magnesium they were considered as protectors against bone fractures.
Introdução: Atualmente, o aumento da expectativa de vida das pessoas reflete a mudança no perfil epidemiológico brasileiro e, uma das maiores consequências enfrentadas devido a esse contexto é o aumento na prevalência de morbidades crônicas, dentre elas, a osteoporose. Essa patologia afeta especialmente as mulheres na pós-menopausa e suas principais consequências são as fraturas, responsáveis por uma elevada morbimortalidade e custos onerosos para o tratamento. No entanto, a nutrição representa um importante papel na formação e manutenção da massa óssea. Considerada como parte do tratamento não farmacológico, a alimentação variada, em qualidade e quantidade, muito provavelmente fornecerá os nutrientes necessários para manter, pelo menos em parte, uma saúde óssea regular durante o envelhecimento. Além disso, pode ser um possível fator de proteção para as principais consequências da osteoporose em idosos. Objetivo: Descrever o consumo alimentar de cálcio, fósforo, magnésio e proteínas em mulheres hospitalizadas por fraturas osteoporóticas em um serviço de Atenção Terciária de um município do interior do Rio Grande do Sul/RS. Metodologia: Estudo caso-controle, composto por 62 mulheres com 55 anos ou mais, sendo 42 no grupo com fraturas e, 20 sem fraturas. Aplicaram-se dois questionários, um contendo identificação, dados clínicos, história social e avaliação antropométrica e, outro para avaliar a ingestão de cálcio, fósforo, magnésio e proteínas, sendo o Questionário Quantitativo de Frequência de Alimentos (QQFA). Resultados: Ingestão de cálcio e magnésio foi significativamente baixa em mulheres com fraturas [446,9 mg/dia vs. 689,90 mg/dia e 135,49 mg/dia e 188,92 mg/dia, respectivamente]. Na análise de regressão logística para fraturas, aumento na ingestão de cálcio e magnésio foi associado com baixo risco para fraturas. Este resultado foi ajustado para idade e IMC. Não houve diferenças na ingestão de proteínas e fósforo entre os grupos. Na análise de regressão logística para fraturas, cálcio e magnésio foram considerados fatores de proteção, enquanto que a idade foi considerada fator de risco para fraturas. Conclusão: Ambos os grupos apresentaram ingestão de cálcio e magnésio bem abaixo das atuais recomendações para sexo e faixa etária. Em relação aos fatores associados às fraturas, ingestão dietética de cálcio e magnésio foi considerada como protetora contra fraturas ósseas.

Background. Oral anticoagulants are associated with a decrease in bone mass density. Our study evaluates the association between an osteoporotic fracture and oral anticoagulants.
Methods. We conducted a case-control study on subjects aged 70 years and older enrolled in the Quebec health insurance plan between 1992 and 1994. Incident cases of an osteoporotic fracture (index event) were identified by ICD-9 codes and surgical procedure codes. Exposure defined as one or more prescriptions of oral anticoagulants dispensed before the index event. Ten controls for each case, matched by age and date of index event, were selected.
Results. Among 1,523 cases, 48 (3.2%) were exposed to oral an anticoagulant; among 15,205 controls, 461 (3.0%) were exposed (adjusted odds ratio: 1.1, 95% CI: 0.8--1.4). These negative results persisted after stratifying the exposure into the cumulative dose and duration of treatment.
Conclusions. Oral anticoagulants are not significantly associated with an osteoporotic fracture in the elderly.

The aim of this thesis was a preliminary investigation of nutritional and biochemical factors which may be implicated in ethnic differences in fracture risk. Investigation of polymorphic loci of the vitamin D receptor gene revealed that the frequency of B and t alleles was considerably greater in the British subjects than in their Gambian or Chinese counterparts (p<0.001). The frequency of the "s" allele of the polymorphic SP1 binding site in the collagen 1α1 gene was also considerably greater in the British subjects than in the Gambian (p<0.02) or Chinese (p<0.001) subjects. The vitamin K status of bone, indicated by the γ-carboxylation of plasma osteocalcin, was determined in eleven premenopausal women of each group and in postmenopausal Gambian (n=50), British (n=31) and Chinese (n=23) subjects. In all groups, undercarboxylation was significantly higher post- than premenopause, but this was related to the higher total osteocalcin concentration present postmenopause. After consideration of differences in total osteocalcin, undercarboxylation was highest in the British, intermediate in the Gambian and lowest in the Chinese subjects irrespective of menopausal status. Possible determinants of osteocalcin γ-carboxylation were investigated. There was a direct relationship between plasma vitamin K concentration and osteocalcin γ-carboxylation in the British subjects, and a direct relationship between plasma triglyceride concentration and osteocalcin carboxylation in the Gambian and Chinese subjects. Apolipoprotein E2 allele was associated with increased γ-carboxylation in the British and Chinese subjects, but there was little indication of a an influence of plasma vitamin D concentration. Differences in plasma vitamin K concentration were observed between the ethnic groups, being significantly higher in the postmenopausal Chinese compared with the British (117% p≤0.0001) and Gambian subjects (103% p≤0.0001). These data suggest genetic differences may exist in calcium homeostasis and the collagen structure of bone, along with differences in vitamin K status and the γ-carboxylation system of osteoblasts, which may be implicated in ethnic variation in osteoporotic fracture risk.