RESUMO
Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
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Anabolizantes , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Anabolizantes/uso terapêutico , Brasil , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/tratamento farmacológico , Densidade ÓsseaRESUMO
ABSTRACT Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.
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Hip fracture incidence rates in three representative geographic areas in Brazil over a period of 2 years (2010-2012) were assessed for the first time. Estimated incidence rates varied regionally, and markedly differed from those previously reported. Thus, national guidelines as well as FRAX Brazil should be revised in light of this new data. PURPOSE: To determine the annual incidence of hip fractures in individuals aged 50 years and over, living in 3 cities located in different regions of the country. To investigate the age, gender, and regional differences in fracture rates. Based on the obtained data, to estimate the national incidence of hip fractures resulting from osteoporosis, in order to improve prevention strategies. METHODS: Retrospective, observational study including all patients aged ≥ 50 years admitted in hospitals because of a hip fracture in three cities (Belem, Joinville, and Vitoria) from representative geographic areas in Brazil from 2010 to 2012. Data were obtained from medical records in those cities. We analyzed incidence rates (crude and age- and gender-standardized rates) for hip fractures. RESULTS: There were 1025 (310 in men and 715 in women) hip fractures in the over 50-year-old merged population from the three cities. The crude incidence rate for hip fracture was 103.3/100,000 (95% confidence interval [CI = 97.0; 109.7), in men 77.4/100,000 (95% CI = 68.8; 86.0), and in women 125.2/100,000 (95% CI = 116.0; 134.4). Incidence standardized for age and gender was 105.9 cases per 100,000 persons per year (95% CI = 99.4; 112.4); 78.5 cases per 100,000 (95% CI = 69.8; 87.3) in men and 130.6 cases 100,000 in women (95% CI = 121.0, 140.2) per year. Belem, located in the equatorial region (latitude 1° 27' S), had significantly lower crude and age-adjusted incidence than Joinville (latitude 26° 18' S) and Vitoria (latitude 20° 19' S), which were no different from each other. The incidence of fractures increased exponentially with age, and women had about twice the risk of fractures than men. CONCLUSIONS: Hip fracture mainly affects elderly women and presents great variability in incidence between the different regions in Brazil. The incidence of hip fractures in Brazil differed markedly from that reported previously, so that national guidelines and the FRAX model for Brazil should be revised.
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Fraturas do Quadril , Osteoporose , Idoso , Brasil/epidemiologia , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Estudos RetrospectivosRESUMO
The Brazilian guidelines for prevention and treatment of glucocorticoid-induced osteoporosis were updated and important topics were included such as assessment of risk fracture using FRAX Brazil, use of denosumab, and also recommendations for the use of glucocorticoid pulse therapy and inhaled glucocortiocoid. INTRODUCTION: Glucocorticoids (GCs) are used in almost all medical specialties and the incidences of vertebral/nonvertebral fractures range from 30 to 50% in individuals treated with GCs for over 3 months. Thus, osteoporosis and frailty fractures should be prevented and treated in patients initiating treatment or already being treated with GCs. The Committee for Osteoporosis and Bone Metabolic Disorders of the Brazilian Society of Rheumatology (BSR) established in 2012 the Brazilian Guidelines for glucocorticoid-induced osteoporosis (GIO). Herein, we provide a comprehensive update of the original guidelines based on improved available scientific evidence and/or expert experience. METHODS: From March to June 2020, the Osteoporosis Committee of the BRS had meetings to update the questions presented in the first consensus (2012). Thus, twenty-six questions considered essential for the preparation of the recommendations were selected. A systematic literature review based on real-life scenarios was undertaken to answer the proposed questions. The MEDLINE, EMBASE, and SCOPUS databases were searched using specific search keywords. RESULTS: Based on the review and expert opinion, the recommendations were updated for each of the 26 questions. We included 48 new bibliographic references that became available after the date of the publication of the first version of the consensus. CONCLUSION: We updated the Brazilian guidelines for the prevention/treatment of GIO. New topics were added in this update, such as the assessment of risk fracture using FRAX Brazil, the use of denosumab, and approaches for the treatment of children and adolescents. Furthermore, we included recommendations for the use of inhaled GCs and GC pulse therapy in clinical settings.
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Conservadores da Densidade Óssea , Fraturas Ósseas , Osteoporose , Reumatologia , Adolescente , Conservadores da Densidade Óssea/uso terapêutico , Brasil , Criança , Glucocorticoides/efeitos adversos , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controleRESUMO
OBJECTIVES: This study evaluated the efficacy and safety of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) therapy. METHODS: In this phase 3, double-blind, 52-week, placebo-controlled study, 290 patients with moderately to severely active RA and inadequate response to MTX were randomly assigned 1:1 to placebo or baricitinib 4-mg once daily, stratified by country (China, Brazil, Argentina) and presence of joint erosions. Primary endpoint measures included American College of Rheumatology 20% response (ACR20) at week 12. Secondary endpoints included changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Disease Activity Score for 28-joint counts (DAS28)-high-sensitivity C-reactive protein (hsCRP), Simplified Disease Activity Index (SDAI) score ≤3.3, mean duration of morning joint stiffness, severity of morning joint stiffness numeric rating scale (NRS 0-10), worst tiredness NRS, and worst joint pain NRS at week 12. RESULTS: Most patients (approximately 80%) were from China. More patients achieved ACR20 response at week 12 with baricitinib than with placebo (58.6% vs. 28.3%; p<0.001). Statistically significant improvements were also seen in HAQ-DI, DAS28-hsCRP, morning joint stiffness, worst tiredness, and worst joint pain in the baricitinib group compared to placebo at week 12. Through week 24, rates of treatment-emergent adverse events, including infections, were higher for baricitinib compared to placebo, while serious adverse event rates were similar between baricitinib and placebo. CONCLUSIONS: In patients with RA who had an inadequate response to MTX, baricitinib was associated with significant clinical improvements as compared with placebo.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Argentina , Azetidinas , Brasil , China , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Purinas , Pirazóis , Sulfonamidas , Resultado do TratamentoRESUMO
BACKGROUND: Current guidelines on the treatment of rheumatoid arthritis (RA) recommend early therapy targeting the achievement of low disease activity (LDA) or clinical remission. Little published information is available on the success of this treatment strategy in Latin America. In a subset analysis of patients from Latin America, we compared efficacy maintenance with etanercept 50âmg once weekly (ETN50) versus placebo (PBO), on a background of methotrexate (MTX)â±âother non-biologic, disease-modifying antirheumatic drugs, in patients with moderate-to-severe RA who had achieved LDA with ETN50. METHODS: In the Treat-to-Target trial, adult patients with active RA nonresponsive to MTX were treated with ETN50 for 24 weeks (Period 1). Patients achieving LDA were randomized to receive ETN50 or PBO for 28 additional weeks (Period 2). The proportion of patients maintaining LDA at week 52 and other efficacy and quality-of-life measures were assessed. Descriptive statistics are presented using last observation carried forward imputation of data. RESULTS: Of the 64 patients from Latin America treated in Period 1, 61 (95.3%) achieved LDA. Among patients receiving ETN50, 13/34 remained in LDA and 6/14 maintained remission at week 52 versus 6/27 and 4/10 patients receiving PBO. The median time to flare was 113 days and 33 days for the ETN50 and PBO groups, respectively. In the overall population, adverse events were reported in 37% and 43%, serious adverse events in 1% and 4%, and serious infections in 0% and 2% of patients in the ETN50 and PBO groups, respectively. CONCLUSIONS: In patients with RA from Latin America, continuing treatment with ETN50 after achieving LDA appears to result in a higher proportion of patients maintaining LDA and remission compared with switching to PBO. CLINICALTRIALS. GOV REGISTRATION: NCT01578850.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Etanercepte/administração & dosagem , Adulto , Antirreumáticos/efeitos adversos , Quimioterapia Combinada , Etanercepte/efeitos adversos , Feminino , Humanos , América Latina , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Qualidade de Vida , Indução de Remissão , Método Simples-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety of tofacitinib in Brazilian patients from Phase 2 (P2) and Phase 3 (P3) global studies of up to 24 months' duration were evaluated. METHODS: Data were pooled from Brazilian patients with RA and an inadequate response to conventional synthetic or biologic disease-modifying antirheumatic drugs enrolled in P2/P3 tofacitinib studies who received tofacitinib 5 or 10âmg twice daily (BID), or placebo, as monotherapy or in combination with methotrexate. Efficacy, safety, and patient-reported outcomes were assessed over 24 months. RESULTS: Patients (226) from Brazil were treated in tofacitinib global P2/P3 studies. At Month 3, there were improvements in American College of Rheumatology 20/50/70 response rates, Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and Health Assessment Questionnaire-Disability Index scores with both tofacitinib doses. Improvements from baseline in pain, fatigue, and health-related quality of life with tofacitinib 5 and 10âmg BID were reported. Efficacy improvements were sustained up to Month 24. The most frequent class of adverse events was infections and infestations. No cases of tuberculosis or other opportunistic infections were reported. CONCLUSION: In a Brazilian subpopulation of patients with RA, tofacitinib reduced disease signs and symptoms and improved physical function up to Month 24, with a safety profile consistent with findings from global studies.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/administração & dosagem , Metotrexato/administração & dosagem , Piperidinas/administração & dosagem , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Sedimentação Sanguínea/efeitos dos fármacos , Brasil , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Janus Quinases/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Resultado do TratamentoRESUMO
Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Imunogenicidade da Vacina , Fatores de Tempo , Brasil , Testes de Inibição da Hemaglutinação , Vacinas contra Influenza/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Reprodutibilidade dos Testes , Fatores Etários , Vacinação/efeitos adversos , Resultado do Tratamento , Hemaglutinação por Vírus/imunologia , Anticorpos Antivirais/sangueRESUMO
The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines. In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18-60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed. A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults. The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.
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Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Adulto , Fatores Etários , Anticorpos Antivirais/sangue , Brasil , Feminino , Testes de Inibição da Hemaglutinação , Hemaglutinação por Vírus/imunologia , Humanos , Vacinas contra Influenza/efeitos adversos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Vacinação/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adulto JovemRESUMO
Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding of the molecular and cellular mechanisms involved in the remodeling process have allowed the development of new targets for osteoporosis treatment. Cathepsin K, a cysteine protease, is found in osteoclasts along the bone resorption surfaces and very efficiently degrades type I collagen, the major component of the organic bone matrix. Inhibition of cathepsin K reduces bone resorption but does not impair bone formation particularly at cortical sites. Odanacatib, a potent and highly selective cathepsin K inhibitor, showed prevention of bone loss without reduction of bone formation in preclinical and clinical trials (phase I and II). Odanacatib is currently in a phase III fracture outcome international trial for the treatment of postmenopausal osteoporosis.
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Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects approximately 1% of the worldwide population. It primarily targets the synovial membrane of joints, leading to a synovial proliferation, joint cartilage lesion and erosions in the adjacent bone tissue. The disease is usually progressive and if the inflammatory process is not adequately suppressed, joint deformity takes place, leading to a significant functional disability and work incapacity. Over the last decade, biological therapy was established as a major step towards disease control in those patients who experienced failure after treatment with disease-modifying antirheumatic drugs. Despite the growing number of biological agents with different immunological targets, a significant number of patients do not receive appropriate disease control, or have the use of these agents limited because of adverse events. As such, the search for new molecules with a higher efficacy and better safety profile is ongoing. This article focuses on a new drug, tofacitinib, which is a synthetic disease-modifying antirheumatic drug for treatment of RA. Preclinical studies in arthritis and transplantation animal models are reviewed as a background for the possible use of tofacitinib treatment in humans. Four Phase II (one A and three B dose-ranging) trials lasting from 6 to 24 weeks in RA patients showed significant American College of Rheumatology 20 improvements as early as week 2 and sustained at week 24 in two studies. Tofacitinib Phase III studies in RA are included in a clinical program called 'ORAL Trials'. Long-term follow-up from ongoing studies will contribute to a more accurate tofacitinib efficacy and safety profile. Trials in other illness such as psoriasis, psoriatic arthritis, renal transplant rejection prevention, inflammatory bowel diseases and dry eye are underway.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Janus Quinase 3/antagonistas & inibidores , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Animais , Artrite Reumatoide/fisiopatologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Piperidinas , Resultado do TratamentoRESUMO
Entre as diversas formas de osteoporose (OP) secundária, a osteoporose induzida pelo uso terapêutico de glicocorticoide (OPIG) se destaca como a mais frequente. Embora os glicocorticoides estimulem a reabsorção óssea, sua ação sobre o osso é melhor caracterizada pela inibição da maturação e da diferenciação dos osteoblastos prejudicando, assim, com maior intensidade a formação óssea. Para o tratamento da OPIG existem evidências para o uso de bisfosfonatos, teriparatida, ranelato de estrôncio e denosumabe, sempre associados ao cálcio e vitamina D. Outras medicações de uso mais restrito na clínica médica também podem induzir OP, sendo que as melhores evidências são para agonistas do hormônio liberador de gonadotrofinas (GnRHa), inibidores de aromatase, anticonvulsivantes e hormônios da tiroide em dose supressiva. Mais recentemente algumas evidências para perda de massa óssea e fraturas surgiram após o uso prolongado de glitazonas e inibidores da bomba de prótons. As melhores evidências para o tratamento da OP secundária induzida por drogas mostram que os bisfosfonatos são a terapêutica mais utilizada. Estudos recentes demonstraram que o denosumabe mostrou eficácia também no tratamento de OP induzida por inibidores da aromatase.
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Descrevemos as posições oficiais da Sociedade Brasileira de Densitometria Clínica (SBDens) para a realização e o relato do exame de densitometria óssea. Essas posições foram obtidas por consenso em encontro realizado em São Paulo no ano de 2006. A SBDens contou com o apoio de várias sociedades científicas descritas no texto.
We describe the official positions of the Brazilian Society for Clinical Densitometry (SBDens) for the performance and report of the bone mineral density testing. These positions were obtained by consensus in a meeting at São Paulo in 2006. SBDens positions were supported by other scientific societies described in the text.
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The use of placebo control groups (e.g., subjects using calcium and vitamin D) in osteoporosis trials with subjects at high risk for fracture has been systematically questioned by institutional review boards (IRBs). Regulatory agencies, on the other hand, continue to not only recommend but also require that placebo-controlled trials be presented for the registration of new drugs for osteoporosis treatment. The Declaration of Helsinki and its updates have upheld the principle that protection of research subjects' rights is of primary concern. Nevertheless, even the Declaration keeps clearly opening the possibility of using placebo-control designs if it is justified for "compelling and scientifically sound methodological reasons." The use of intermediary endpoints or surrogates to establish the efficacy or safety of new medications in the management of osteoporosis is currently considered scientifically insufficient. This concept has led regulatory agencies, such as the Food and Drug Administration in the United States and the European Medicines Agency in the European Union, to require "fragility fracture reduction" as the primary endpoint in clinical trials for the registration of new drugs. Superiority or noninferiority trials are alternatives to placebo-controlled designs. However, factors such as sample size, cost, and statistical limitations render these models impractical for the registration of new medications for osteoporosis. We recommend collaboration among regulatory agencies, IRBs, scientists, and ethicists on the design of clinical trials for the registration of new medications for reduction of fracture risk. Delay in developing mutually acceptable models may impair scientific development in the field and possibly deprive patients of potentially beneficial treatments.
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Ensaios Clínicos Controlados como Assunto/ética , Osteoporose/tratamento farmacológico , Placebos , Cálcio da Dieta/uso terapêutico , Fraturas Ósseas/prevenção & controle , Humanos , Consentimento Livre e Esclarecido , Metanálise como Assunto , Direitos do Paciente , Segurança , Vitamina D/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the inter- and intrareader variability for interpretation of a modified Larsen's radiographic classification system for juvenile rheumatoid arthritis (JRA) focused on osteochondral lesions and a conventional Larsen's classification system, compared to a reference MR scoring system of corresponding images. MATERIALS AND METHODS: Seventy-five radiographs of 60 children with JRA, performed within a short interval of time from the MR examinations, were independently evaluated by three experienced radiologists, three diagnostic imaging residents and three rheumatologists, in two separate sessions, according to the two different classification methods, blinded to the corresponding MR images. RESULTS: The inter- and intrareader concordance rates between the two radiographic classification systems and the MR-related radiographs were respectively poor and poor/moderate. The interobserver range of weighted kappa values for the conventional and the modified Larsen's system respectively was 0.25-0.37 vs 0.19-0.39 for radiologists, 0.25-0.37 vs 0.18-0.30 for residents and 0.19-0.51 vs 0.17-0.29 for rheumatologists. The intrareader rate ranged from 0.17-0.55 for radiologists, 0.2-0.56 for residents, and 0.14-0.59 for rheumatologists. CONCLUSION: Although the proposal of a new radiographic classification system for JRA focused on osteochondral abnormalities sounds promising, the low inter- and intrareader concordance rates with an MR-related radiographic system makes the clinical applicability of such a radiographic system less suitable.
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Artrite Juvenil/classificação , Artrite Juvenil/diagnóstico por imagem , Adolescente , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Criança , Pré-Escolar , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Masculino , Variações Dependentes do Observador , RadiografiaRESUMO
A artrite reumatóide é uma doença bastante frequente, que pode apresentar evoluçäo progressiva em um grande número de pacientes. Alteraçöes radiológicas de estruturas articulares podem ser observadas nos dois primeiros anos da doença. Após 5 a 10 anos de seu início, parte dos pacientes apresenta deterioraçäo do estado funcional, incapacidade progressiva para o trabalho e evoluçäo das lesöes radiológicas. Morte prematura pode ocorrer tanto pela própria doença quanto pelas comorbidades. Estas evidências têm mudado a visäo tradicional do prognóstico da artrite reumatóide, propondo que um tratamento mais agressivo talvez seja mais coerente com a evoluçäo observada a médio e longo prazo. Novas opçöes terapêuticas têm surgido e prometem revolucionar o tratamento dos pacientes com artrite reumatóide
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Artrite Reumatoide , Terapia BiológicaRESUMO
BACKGROUND: The aim of this study was to determine the relationship between habitual physical activity (HPA) during life and bone mineral density (BMD) in men aged 50 years and older. METHODS: A total of 326 men aged 50 years and older, volunteers living in São Paulo city, Brazil, were studied. BMD was measured in the whole body, femoral neck, Ward's triangle, trochanter, and lumbar spine (L2-L4) with a dual-energy x-ray absorptiometer. The HPA data were collected with questionnaires inquiring about physical exercise and occupational physical activity in the past and during the past 12 months and leisure and locomotor physical activity in the preceding 12 months. The relationship between BMD and HPA was analyzed using multiple linear regression models adjusted for age and body mass index (BMI). RESULTS: Practice of physical exercise in the past 10-20 years and leisure and locomotor physical activity in the preceding 12 months showed a significant positive correlation with BMD of whole body, femoral neck, trochanter, and lumbar spine, and this association was independent of age and BMI. CONCLUSIONS: HPA can contribute to preserving BMD in men aged 50 years and older in Brazil, when it is practiced in the past 10-20 years and even in the present.
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Densidade Óssea/fisiologia , Exercício Físico/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Brasil/epidemiologia , Estudos Transversais , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estatística como AssuntoRESUMO
A hipoplasia de medula óssea é um efeito colateral incomum do uso de maetotrexato (MTX), em baixas doses, na artrite reumatóide (AR). Fatores de risco para essa complicação são: Hipoalbuminemia, queda do clearance de creatinina, alcoolismo, idade avançada e uso de certas drogas, como a ranitidina ou sulfametoxazol-trimetoprim. Os autores não encontraram relatos desse efeito adverso no lúpus eritematoso sistêmico e apresentam um caso de hipoplasia de medula óssea em paciente com LES em atividade, que estava sendo tratado com baixas doses de MTX. Discutem, também, os fatores de risco para essa complicação
Assuntos
Humanos , Feminino , Adulto , Doenças da Medula Óssea/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , MetotrexatoRESUMO
Objetivo: Relatar e discutir os casos de pacientes com artrite reumatóide (AR) que fizeram uso de difosfato de cloroquina e desenvolveram retinopatia. Método: Revisão de prontuários de todos os pacientes com artrite reumatóide, que tomaram difosfato de cloroquina, atendidos no ambulatório do Hospital Heliópolis no período de 1986 a 1998 (13 anos) e que tiveram o exame oftalmológico documentado. Resultados: De 165 pacientes que receberam difosfato de cloroquina foram identificados quatro (2,4 por cento) que apresentaram retinopatia pela avaliação oftalmológica. Destes, todos estavam recebendo 250 mg por dia com dose média abaixo de 4 mg/Kg/dia, sendo que a dose cumulativa variou de 127g a 635g. O tempo de uso variou entre 1,5 e 7 anos. Conclusão: O diagnóstico de retinopatia causada pelo difosfato de cloroquina ainda é um desafio, principalmente na foram precoce Muitos pacientes recebem o diagnóstico de provável retinopatia pela cloroquina com alterações mínimas e inespecíficas e isto leva a uma descontinuação da droga. O difosfato de cloroquina pode ser usado com segurança desde que na dose preconizada e que se façam exames oftalmológicos periódicos, preferencialmente, a cada seis meses