ABSTRACT
Osteoporosis and vertebral and non-vertebral fractures are common in glucocorticoids (GC) treated patients. Oral GC treatment leads to bone loss, particularly of trabecular bone. The benefits of GC used in rheumatological and traumatological disorders are known but they would have possible negative effects on bone. This systematic review aimed to evaluate the effects of epidural steroid injections (ESI), and intra-articular and intramuscular GC administration on bone mineral density (BMD) and fragility fractures. A systematic review of Medline/PubMed, Cochrane, and LILACS up to November 2020 was conducted. Meta-analyses, systematic reviews, randomized and non-randomized controlled trials, and prospective and retrospective studies comparing the effect of ESI, intra-articular or intramuscular GC used compared to a control group or baseline measurements were included. Results: A total of 8272 individuals were included among the 13 selected articles (10 about ESI and 3 about intra-articular GC; no article was found evaluating intramuscular GC). Only a few studies showed a negative effect of ESI on bone in the qualitative analysis considering osteopenia and osteoporosis in lumbar spine, femoral neck and total hip and BMD as surrogate outcomes. On the other hand, the qualitative analysis showed that most studies found an increased risk of fragility fracture. However, only two studies could be included in the quantitative analysis, in which there were no differences between patients exposed to ESI versus controls in all evaluated regions. In conclusion, there was insufficient evidence to suggest that ESI and intra-articular GC, unlike oral GC, negatively affect bone mass. Longitudinal studies are needed to obtain more knowledge regarding the effect of ESI or intra-articular GC on BMD and fragility fractures. (AU)
La osteoporosis y las fracturas vertebrales y no vertebrales son comunes en pacientes tratados con glucocorticoides (GC). El tratamiento oral con GC conduce a la pérdida ósea, particularmente del hueso trabecular. Los beneficios de los GC utilizados en patologías reumatológicas y traumatológicas son conocidos, pero tendrían posibles efectos negativos sobre el hueso. Esta revisión sistemática tuvo como objetivo evaluar los efectos de las inyecciones epidurales de esteroides (ESI), GC intraarticulares e intramusculares sobre la densidad mineral ósea (DMO) y las fracturas por fragilidad. Se realizó una revisión sistemática de Medline/PubMed, Cochrane y LILACS hasta noviembre de 2020. Se incluyeron metanálisis, revisiones sistemáticas, ensayos controlados aleatorizados y no aleatorizados, estudios prospectivos y retrospectivos que compararon el efecto de ESI, GC intraarticular o intramuscular utilizado en comparación con un grupo de control o mediciones iniciales. Resultados: Se incluyeron un total de 8272 individuos entre los 13 artículos seleccionados (10 sobre ESI y 3 sobre GC intraarticular; no se encontró ningún artículo que evaluara GC intramuscular). Solo unos pocos estudios mostraron un efecto negativo del ESI sobre el hueso en el análisis cualitativo considerando la osteopenia y la osteoporosis en la columna lumbar, el cuello femoral y la cadera total y la DMO como un resultado indirecto. Por otro lado, el análisis cualitativo mostró que la mayoría de los estudios encontraron un mayor riesgo de fractura por fragilidad. Sin embargo, solo dos estudios pudieron incluirse en el análisis cuantitativo, en los que no hubo diferencias entre los pacientes expuestos a ESI versus los controles en todas las regiones evaluadas. En conclusión, no hallamos datos suficientes para sugerir que la ESI y los GC intraarticulares, a diferencia de los GC orales, afectan negativamente a la pérdida ósea. Se necesitan estudios longitudinales para obtener más conocimiento sobre el efecto de ESI o GC intraarticular en la DMO y las fracturas por fragilidad. (AU)
Subject(s)
Humans , Osteoporosis/etiology , Bone Diseases, Metabolic/etiology , Bone Density/drug effects , Osteoporotic Fractures/chemically induced , Glucocorticoids/adverse effects , Review Literature as Topic , Bias , Drug Administration Routes , Meta-Analysis as Topic , Clinical Trials as Topic , Risk Assessment , Densitometry , Estrogens/adverse effectsABSTRACT
ABSTRACT Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.
RESUMO Com base na vasta experiência de uso, segurança e eficácia comprovada na redução de fraturas vertebrais, não vertebrais e femorais, os bisfosfonatos são considerados agentes de primeira linha no tratamento da osteoporose pós-menopáusica. No entanto, os relatos pós-venda baseados no tratamento de milhões de pacientes/ano durante períodos prolongados de tempo revelaram a ocorrência de efeitos adversos inicialmente inesperados, como osteonecrose da mandíbula e fratura atípica do fêmur. Isso levou as agências reguladoras globais a restringirem a duração do tratamento com bisfosfonatos. No entanto, apesar da associação entre esses efeitos e os bisfosfonatos, esse risco deve ser analisado no contexto do tratamento da osteoporose, paralelamente ao benefício na prevenção de fraturas osteoporóticas e suas consequências clínicas. Portanto, considera-se plausível discutir a restrição ao uso dos bisfosfonatos, possíveis indicações para o tratamento prolongado e terapias opcionais após a suspensão dessa classe de fármaco para pacientes com alto risco persistente de fratura após o tratamento inicial, especialmente se considerarmos os problemas financeiros de saúde pública no Brasil e a escassez de fármacos fornecidos pelo governo. Assim, para padronizar o tratamento da osteoporose no sistema público de saúde pretende-se desenvolver uma proposta de tratamento farmacológico cientificamente fundamentada para a osteoporose pós-menopáusica, estabelecer critérios de indicação e permitir o uso racional de cada agente farmacológico. Discutem-se a duração do tratamento inicial com bisfosfonatos, as opções terapêuticas para pacientes refratários e potenciais indicações de outras classes de medicamentos como tratamento de primeira linha na esfera da saúde pública, em que a avaliação do risco e custo-efetividade é uma prioridade.
Subject(s)
Humans , Osteoporosis, Postmenopausal/drug therapy , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Clinical Decision-Making/methods , Algorithms , Brazil , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/economics , Risk Factors , Cost-Benefit Analysis , Diphosphonates/economics , Bone Density Conservation Agents/economics , Osteoporotic Fractures/economics , Osteoporotic Fractures/chemically induced , Osteoporotic Fractures/prevention & control , Bisphosphonate-Associated Osteonecrosis of the Jaw/economics , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , National Health ProgramsABSTRACT
La osteoporosis inducida por glucocorticoides (OIC) es la causa más común de osteoporosis secundaria. La pérdida ósea se produce en forma temprana, en los primeros meses siguientes a la introducción de los glucocorticoides (GC), dependiendo de la dosis diaria. La patogénesis es multifactorial y el principal efecto deletéreo es la inhibición de la formación ósea. Los GC inducen fracturas por fragilidad ósea, especialmente en la columna vertebral, y esto genera incapacidad funcional. En los últimos años se han publicado algunas guías internacionales elaboradas por consenso para la prevención y el tratamiento de la OIC. La Sociedad Argentina de Osteoporosis designó a un grupo de trabajo para elaborar una guía propia y actualizada para el diagnóstico, la prevención y el tratamiento de la OIC (GE-OIC-SAO). (AU)
Glucocorticoid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis. It occurs early, with rapid bone loss in the first few weeks after the initiation of the treatment, with a rate that is dependent mainly on the daily dose. While the pathogenesis is multifactorial, the highest inhibitory effect occurs on bone formation. Glucocorticoids induce fragility fractures, especially in spine, generating functional disability. In recent years, there have been some international guidelines developed by consensus for the prevention and treatment of GIO. The Argentinean Osteoporosis Society appointed a working group to prepare a national guide updating the diagnosis, prevention and treatment of GIO. (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Osteoporosis/diagnosis , Osteoporosis/chemically induced , Osteoporosis/prevention & control , Osteoporosis/drug therapy , Osteoporosis/therapy , Glucocorticoids/adverse effects , Osteogenesis Imperfecta/chemically induced , Osteoporosis/physiopathology , Osteoporosis/epidemiology , Vitamin D/administration & dosage , Calcium/administration & dosage , Practice Guidelines as Topic , Teriparatide/administration & dosage , Densitometry , Diphosphonates/administration & dosage , Vertebroplasty , Osteoporotic Fractures/chemically induced , Glucocorticoids/administration & dosageABSTRACT
BACKGROUND/AIMS: We investigated differences in identifying candidates for antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two available clinical guidelines. METHODS: We prospectively enrolled 100 female patients aged 50 years or older with RA who visited Hanyang University Hospital for periodic examinations between April 2011 and August 2011. We applied the glucocorticoid-induced osteoporosis (GIOP) recommendations and the National Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement between the guidelines for identifying candidates for antiosteoporotic treatment. We also analyzed the impact of screening vertebral fractures (VFs) in determining the treatment of osteoporosis in RA patients. RESULTS: The 57 patients taking glucocorticoids were classified into high-risk (n = 23), medium-risk (n = 16), and low-risk (n = 18) groups according to the GIOP recommendations. Based on the NOF guidelines, 36 of 57 patients were candidates for antiosteoporotic treatment and the agreement between two guidelines was high (kappa = 0.76). Two of the 18 patients in the low-risk group and 19 of 43 patients not eligible per the GIOP recommendations were classified as candidates for antiosteoporotic treatment by the NOF guidelines. CONCLUSIONS: In determining antiosteoporotic treatment for RA patients, using only the GIOP recommendations is insufficient. Application of the NOF guidelines in patients not eligible for or classified into the low-risk group per the GIOP recommendations and screening for VFs may be helpful in deciding on antiosteoporotic treatment in RA patients.