Реферат
Abstract Multiple myeloma (MM) is a hematological malignancy characterized by unregulated and clonal proliferation of plasma cells in the bone marrow; these cells produce and secrete an anomalous monoclonal immunoglobulin, or a fragment of this, called M protein. The clinical manifestations of MM result from the proliferation of these plasmocytes, the excessive production of monoclonal immunoglobulin and the suppression of normal humoral immunity, leading to hypercalcemia, bone destruction, renal failure, suppression of hematopoiesis and humoral immunity, increasing the risk for the development of infections. The increase in life expectancy of the world population led to a concomitant increase in the prevalence of MM, a pathology that usually affects the elderly population. The aim of this review is to update the reader on epidemiology, diagnostic criteria, differential diagnosis with other monoclonal gam-mopathies, systemic treatment and prognosis of MM.
Resumo O mieloma múltiplo (MM) constitui neoplasia maligna de origem hematológica caracterizada pela proliferação desregulada e clonal de plasmócitos na medula óssea; estas células produzem e secretam imunoglobulina monoclonal anômala, ou um fragmento desta, denominado proteína M. As manifestações clínicas do MM decorrem da proliferação destes plasmócitos, da produção excessiva de imunoglobulina monoclonal e da supressão da imunidade humoral normal, levando à hipercalcemia, destruição óssea, insuficiência renal, supressão da hematopoiese e da imunidade humoral,aumentandooriscoparaodesenvolvimento de infecções. O aumento na expectativa de vida da população mundial levou a concomitante incremento na prevalência do MM, patologia que habitualmente acomete a população idosa. O objetivo desta revisão é atualizar o leitor sobre a epidemiologia, critérios diagnósticos, diagnóstico diferencial com outras gamopatias monoclonais, tratamento sistêmico e prognóstico do MM.
Тема - темы
Humans , Male , Female , Orthopedic Procedures , Diphosphonates/therapeutic use , Prophylactic Surgical Procedures , Fractures, Spontaneous/diagnostic imaging , Multiple Myeloma/radiotherapyРеферат
Abstract Objective The present study aims to describe outcomes from a series of surgically treated patients with atypical femoral fracture due to bisphosphonates use, in addition to correlate the time of previous medication use with fracture consolidation time, and to compare the consolidation time of complete and incomplete fractures. Methods This is an observational, retrospective study with 66 patients diagnosed with atypical femur fractures associated with chronic bisphosphonates use. The patients underwent orthopedic surgical treatment at a referral hospital from January 2018 to March 2020. Results All patients were females, with two bilateral cases. Fracture consolidation occurred in all cases, with an average time of 2.3 months and a follow-up time of 5.8 months. The average time of bisphosphonates use was 7.8 years. There was no correlation between the time of previous bisphosphonates use and the time for fracture consolidation. Consolidation time differed in complete and incomplete fractures. Conclusion Surgical treatment with a long cephalomedullary nail resulted in consolidation in all patients. The consolidation time was longer in complete fractures when compared with incomplete lesions, and there was no correlation between the time of previous bisphosphonates use and the consolidation time . Level of evidenceLevel IV, case series
Resumo Objetivo Descrever os resultados de uma série de pacientes tratados cirurgicamente com diagnóstico de fratura femoral atípica associada ao uso de bisfosfonatos, assim como correlacionar o tempo de uso prévio da medicação com o tempo de consolidação da fratura e comparar o tempo de consolidação das fraturas completas e incompletas. Métodos Trata-se de um estudo observacional e retrospectivo de 66 pacientes com diagnóstico de fratura atípica do fêmur associada ao uso crônico de bisfosfonatos. Os pacientes foram submetidos ao tratamento cirúrgico ortopédico em hospital de referência no período de janeiro de 2018 a março de 2020. Resultados Os pacientes incluídos no estudo eram todos do sexo feminino, com dois casos bilaterais. A consolidação da fratura ocorreu em todos os casos com tempo médio de 2,3 meses e seguimento de 5,8 meses. O tempo médio de uso de bisfosfonatos foi de 7,8 anos. Não houve correlação do tempo de uso prévio de bisfosfonatos com o tempo de consolidação das fraturas. Houve uma diferença do tempo de consolidação entre as fraturas completas e incompletas. Conclusão Houve consolidação após tratamento cirúrgico com haste cefalomedular longa em todos os pacientes do presente estudo, sendo o tempo de consolidação maior nas fraturas completas em relação às incompletas, e não houve correlação entre o tempo de uso prévio de bisfosfonatos e o tempo de consolidação. Nível de evidênciaNível IV, série de casos
Тема - темы
Humans , Female , Osteoporosis/therapy , Diphosphonates/therapeutic use , Femoral Fractures/surgeryРеферат
Las neoplasias malignas de la cavidad oral en gran medida (90%) consisten en carcinoma de células escamosas que surgen de la mucosa de revestimiento. El 10% restantes de neoplasias malignas orales de un grupo heterogéneo de tumores de diferente etiología. Presentamos dos casos de patología oncohematológica: Mieloma Múltiple (AU)
Malignant neoplasms of the oral cavity largely (90%) consist of squamous cell carcinoma arising from the lining mucosa. e remaining 10% of oral malignancies from a heterogeneous group of tumors of different etiology. We present two cases of oncohematological pathology: Multiple Myeloma (AU)
Тема - темы
Humans , Male , Middle Aged , Plasmacytoma/diagnosis , Plasmacytoma/pathology , Plasmacytoma/diagnostic imaging , Mouth Neoplasms/diagnosis , Radiotherapy , Biopsy/methods , Tomography, X-Ray Computed , Oral Surgical Procedures/methods , Diphosphonates/therapeutic use , Maxillary Sinus/surgery , Multiple MyelomaРеферат
La osteoporosis de la posmenopausia es una enfermedad crónica y progresiva asociada con un bajo pico de masa ósea o una rápida y persistente pérdida de masa ósea como con-secuencia del déficit de estrógenos endógenos y del envejecimiento. A pesar de que en la actualidad la oferta de medicamentos para su tratamiento en distintas etapas de la vida es muy importante, sigue siendo una enfermedad subdiagnosticada y subtratada a nivel global. La edad, las comorbilidades existentes, los tratamientos concomitantes, el riesgo de caídas, y los antecedentes familiares o personales de fracturas recientes o pasadas tanto como la densidad mineral ósea son factores que deben ser considerados en la evaluación de cada paciente para determinar el grado de riesgo de fractura En aquellos considerados con alto riesgo o riesgo inminente de fractura se recomienda iniciar un tratamiento con algún agente anabólico seguido por un anticatabólico para lograr una rápida reducción del riesgo de fractura. Por último, una adecuada adherencia en el tiempo al tratamiento es clave para alcanzar la mayor eficacia terapéutica dirigida a la reducción de la ocurrencia de fracturas por fragilidad ósea. (AU)
Postmenopausal osteoporosis is a chronic and progressive disease associated with low peak bone mass or a fast and persistent loss of bone mass as a consequence of endogenous estrogen deficiency and aging, and it is an underdiagnosed and undertreated disease worldwide. At present, there is a wide range of drugs available for the treatment of postmenopausal osteoporosis, with appropriate treatments for each phase of this stage of a woman's life. All factors that may increase the risk of bone fragility fracture should be considered at the time of patient assessment. These include age, existing comorbidities, concomitant treatments, risk of falling, family history of fractures or recent or past personal history of fractures, and the results of bone mineral density assessment. In those patients at high risk or imminent risk of fracture, it is recommended to start treatment with an anabolic agent followed by an anticatabolic agent, in order to achieve an immediate reduction of fracture risk. Finally, an adequate adherence to treatment over time will allow achieving the greatest effectiveness of the proposed therapy, which is the reduction of bone fragility fracture events. (AU)
Тема - темы
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Osteoporosis, Postmenopausal/drug therapy , Treatment Outcome , Fractures, Bone/prevention & control , Medication Adherence , Bone Density , Risk Factors , Teriparatide/therapeutic use , Risk Reduction Behavior , Diphosphonates/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Healthy LifestyleРеферат
Con el advenimiento de la terapia antirretroviral, el pronóstico y la sobrevida de los pacientes infectados con el virus de la inmunodeficiencia humana (VIH) han cambiado de manera radical, por lo cual en la actualidad se evidencia un aumento en el riesgo de padecer enfermedades no relacionadas con el VIH como, por ejemplo, la osteoporosis. La disminución de la densidad mineral ósea (DMO) se observa en el 40-90% de las personas infectadas por el VIH, con una prevalencia de osteopenia y osteoporosis del 52 y 15%, respectivamente. Esta población de pacientes tiene un mayor riesgo de fracturas (60%) en comparación con personas no infectadas y un riesgo de fracturas vertebrales 2,3 veces mayor que en la población general. El tenofovir fumarato se asoció con un aumento de pérdida renal de fósforo e hiperparatiroidismo secundario. El efavirenz y los inhibidores de proteasas (IP) afectan el metabolismo de la vitamina D; actúan a nivel enzimático aumentando la expresión de la enzima CYP24 que lleva a producción de vitamina D inactiva. El FRAX es una herramienta sencilla y accesible, por lo que su uso está recomendado en pacientes con VIH. Además de las medidas higiénico-dietéticas, actividad física, calcio y vitamina D, el uso de bifosfonatos está indicado en el tratamiento de la osteoporosis en estos pacientes. (AU)
With the advent of antiretroviral therapy, the prognosis and survival of patients infected with the human immunodeficiency virus (HIV) have radically changed, which is why there is now evidence of an increased risk of suffering from diseases not related to HIV such as osteoporosis. The decrease in bone mineral density (BMD) is observed in 40-90% of people infected with HIV, with a prevalence of osteopenia and osteoporosis of 52 and 15%, respectively. This patient population has a 60% higher risk of fractures compared to uninfected people and a risk of vertebral fractures 2.3 times higher than in the general population. Tenofovir fumarate administration is associated with increased renal phosphorus loss and secondary hyperparathyroidism. Efavirenz and protease inhibitors (IP) affect the metabolism of vitamin D, they act at the enzymatic level by increasing the expression of the CYP24 enzyme that leads to the production of inactive vitamin D. The FRAX is a simple and accessible tool, so its use is recommended in patients with HIV and in addition to dietary hygiene measures, physical activity, calcium, and vitamin D, the use of bisphosphonates is indicated in the treatment of osteoporosis in these patients. (AU)
Тема - темы
Humans , Male , Female , Osteoporosis/prevention & control , Bone Diseases, Metabolic/prevention & control , Bone Density/drug effects , HIV Infections/complications , Osteoporosis/etiology , Osteoporosis/drug therapy , Protease Inhibitors/adverse effects , Vitamin D/metabolism , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/drug therapy , HIV Infections/drug therapy , HIV , Diphosphonates/therapeutic use , Fractures, Bone/prevention & control , Tenofovir/adverse effectsРеферат
Tecnologia: Teriparatida, comparada a bifosfonados orais ou Raloxifeno. Indicação: prevenção de fraturas em pessoas com osteoporose. Pergunta: A Teriparatida é mais eficaz e segura que os bifosfonados orais ou o Raloxifeno para tratamento da osteoporose e prevenção de fraturas secundárias à osteoporose? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews version 2 (AMSTAR-2). Resultados: Foram selecionadas 2 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: Para a população em geral com osteoporose, a Teriparatida evita mais fraturas vertebrais que o Alendronato de sódio ou Risedronato de sódio, mas efeito similar para fraturas não vertebrais. Teriparatida previne mais fraturas vertebrais e não vertebrais que Raloxifeno. Teriparatida tem maior efeito sobre a massa óssea corporal que o Risedronato de sódio e o Raloxifeno, mas tem efeito similar ao Alendronato de sódio. Na população masculina com osteoporose, a terapia com bifosfonados orais é mais eficaz que suplementação nutricional ou placebo para prevenir fraturas. Já o tratamento com Teriparatida não é mais eficaz que a suplementação nutricional ou placebo
Teriparatide compared to oral bisphosphonates or Raloxifene. Indication: prevention of fractures in people with osteoporosis. Question: Is Teriparatide more effective and safer than oral bisphosphonates or Raloxifene for treating osteoporosis and preventing fractures secondary to osteoporosis? Methods: Bibliographic survey was carried out in the PUBMED database, following predefined search strategies. Evaluation of the methodological quality of systematic reviews was carried out using the tool Assessing the Methodological Quality of Systematic Reviews version 2 (AMSTAR-2). Results: Two systematic reviews were selected, which met the inclusion criteria. Conclusion: For the general population with osteoporosis, Teriparatide prevents more vertebral fractures than Alendronate or Risedronate sodium, but has similar effect for non-vertebral fractures. Teriparatide prevents more vertebral and non-vertebral fractures than Raloxifene. Teriparatide has a greater effect on body bone mass than Risedronate sodium and Raloxifene, but it has a similar effect to Alendronate sodium. In the male population with osteoporosis, oral bisphosphonates is more effective than nutritional supplementation or placebo to prevent fractures. Treatment with teriparatide is no more effective than nutritional supplementation or placebo
Тема - темы
Humans , Teriparatide/therapeutic use , Raloxifene Hydrochloride/therapeutic use , Diphosphonates/therapeutic use , Osteoporotic Fractures/drug therapy , Efficacy , Spinal Fractures/drug therapy , Alendronate/therapeutic use , Evidence-Based Medicine , Risedronic Acid/therapeutic use , Denosumab/therapeutic use , Hip Fractures/drug therapyРеферат
La fosfatasa alcalina baja o hipofosfatasemia, ya sea debida a causas genéticas (hipofosfatasia) o secundarias, presenta correlato clínico. Nuestro objetivo es estimar la prevalencia de hipofosfatasemia crónica persistente y describir sus hallazgos osteometabólicos. Se realizó una búsqueda electrónica de afiliados adultos al Hospital Italiano de Buenos Aires, entre 2013 y 2017, con al menos 2 determinaciones de fosfatasa alcalina igual a 30 UI/l o menor y ninguna mayor de 30 UI/l (rango de referencia 30-100 UI/l). Se excluyeron aquellos con causas secundarias diagnosticadas y se analizaron los correlatos clínico y bioquímico. Se detectó hipofosfatasemia crónica persistente en 78 de 105.925, 0,07% (0,06-0,09) de los afiliados. Solo uno fue excluido por tener causa secundaria. Eran 61,1% mujeres de 44 (34-56) años, fosfatasa alcalina 24 (20-27) UI/L, fosfatemia 4,1 (3,8-4,6) mg/dl. Se observaron osteoartritis, calcificaciones vasculares y fracturas, menos frecuentemente litiasis renal, calcificación del ligamento longitudinal común anterior, pérdida dental y convulsiones. El 63,6% tenían al menos una de las características clínico-radiológicas evaluadas, pero en solo 5,2% fue mencionado el diagnóstico de hipofosfatasemia en la historia clínica. La densitometría evidenció algún grado de afección (osteopenia u osteoporosis) en 76,2%. Se constataron 19 fracturas, con predominio en radio. La prevalencia de hipofosfatasemia fue similar a lo previamente reportado. El reconocimiento fue bajo; sin embargo, se observaron variadas manifestaciones músculo-esqueléticas, similares a las descriptas en la hipofosfatasia del adulto, por lo cual ante una hipofosfatasemia sin causa secundaria se sugiere considerar este diagnóstico. (AU)
Low alkaline phosphatase (ALP) or hypophosphatasemia either due to genetic (hypophosphatasia) or secondary causes, presents a clinical correlate. Our objectives are to estimate the prevalence of persistent hypophosphatasemia and to describe the clinical findings. We performed a search using the electronic medical records of the members of the Hospital Italiano de Buenos Aires health care system, between 2013 and 2017. Adult members with ≥ 2 ALP ≤ 30 IU/l, no ALP >30 IU/l (normal range 30-100 UI/l) and without diagnosed secondary causes were analyzed. Persistent hypophosphatasemia was detected in 78 of 105.925, 0.07% (0.06-0.09) of members. Only one was excluded due to a secondary cause, 61.1% were women, 44 (34-56) year-old, ALP 24 (20-27) IU/l and phosphatemia 4.1 (3.8-4.6) mg/dl. Osteoarthritis, vascular calcifications and fractures were detected, and nephrolithiasis, DISH (Diffuse idiopathic skeletal hyperostosis), tooth loss, and seizures were less frequently observed. At least one of the mentioned characteristics were present in 63.6 %, but only 5.2% had hypophosphatasemia registered in their clinical record. Densitometry showed osteopenia or osteoporosis in 76.2%. There were 19 fractures, most of them in radius. The prevalence of hypophosphatasemia was similar to what has been previously reported. Hypophosphatasemia finding in medical records was low, but far from being asymptomatic, clinical manifestations were observed. In the presence of hypophosphatasemia without a secondary cause, adult hypophosphatasia should be uspected. (AU)
Тема - темы
Humans , Male , Female , Adult , Middle Aged , Aged , Muscle, Skeletal/pathology , Hypophosphatasia/etiology , Osteoporosis/etiology , Bone Diseases, Metabolic/etiology , Bone Density , Prevalence , Cross-Sectional Studies , Hypophosphatemia/diagnosis , Hypophosphatemia/etiology , Diphosphonates/therapeutic use , Alkaline Phosphatase/deficiency , Alkaline Phosphatase/physiology , Alkaline Phosphatase/blood , Osteoporotic Fractures/etiology , Hypophosphatasia/diagnosis , Hypophosphatasia/geneticsРеферат
ABSTRACT Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.
Тема - темы
Humans , Female , Osteoporosis, Postmenopausal , Diphosphonates/therapeutic use , Quality of Life , Alendronate , Bone Density Conservation Agents/therapeutic useРеферат
La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria, producida por una mutación activadora del gen GNAS, responsable de codificar la unidad a-estimuladora de la proteína G (Gsa). La presentación clínica de la enfermedad es muy variada, pues adopta desde formas asintomáticas hasta otras marcadamente sintomáticas. En los últimos años, el análisis exhaustivo de bases de datos de pacientes con DF ha permitido conocer más sobre su historia natural. En este artículo se revisa la información actualmente disponible sobre algunos aspectos que ayudarán al mejor enfoque clínico del paciente, como son: la utilidad clínica de los marcadores óseos, los factores pronósticos para el desarrollo de fracturas, la DF como condición predisponente para el desarrollo de tumores específicos, nuevas perspectivas sobre la fisiopatología del dolor óseo y nuevas estrategias terapéuticas. Un mayor conocimiento sobre la historia natural de esta enfermedad finalmente redundará en la mejor calidad de vida de los pacientes con DF. (AU)
Fibrous dysplasia (FD) is an infrequent, non-hereditary bone disease caused by a somatic mutation of the GNAS gene, responsible for encoding the a-subunit of the G-protein (Gsa). The clinical presentation of the disease varies greatly, with some patients being asymptomatic and others markedly symptomatic. The exhaustive analysis of the database from patients with FD has allowed to learn more about the natural history of this disease. This article reviews the current information available on the clinical utility of bone markers, the prognostic factors for the occurrence of fractures, the evidence supporting as a predisposing condition for the development of specific tumors, new perspectives on the pathophysiology of bone pain, and emerging therapeutic strategies. A greater understanding of the natural history of this disease will allow to make better medical decisions, which will ultimately contribute to improve FD patients' quality of life. (AU)
Тема - темы
Humans , Musculoskeletal Pain/physiopathology , Fibrous Dysplasia of Bone/etiology , Quality of Life , Tamoxifen/therapeutic use , Breast Neoplasms/complications , Breast Neoplasms/drug therapy , Biomarkers , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Diphosphonates/therapeutic use , Fractures, Bone/complications , Fractures, Bone/prevention & control , Musculoskeletal Pain/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Fibrous Dysplasia of Bone/diagnosis , Fibrous Dysplasia of Bone/physiopathology , Fibrous Dysplasia of Bone/therapy , Denosumab/administration & dosage , Denosumab/therapeutic use , Narcotics/therapeutic useРеферат
Introducción: Los bifosfonatos evolucionaron como el pilar para el tratamiento de la osteoporosis, reduciendo la incidencia de fracturas. Recientemente, varias publicaciones describieron la aparición de fracturas atípicas de fémur de baja energía asociadas con el uso de bifosfonatos. El objetivo de este estudio fue evaluar el tiempo promedio de consolidación de las fracturas atípicas de fémur asociadas al tratamiento con bifosfonatos comparado con el de un grupo de control. Materiales y Métodos: Se evaluó, en forma retrospectiva, a 34 mujeres (edad promedio 74 años) con fracturas atípicas; 16 de ellas habían recibido bifosfonatos, al menos, por cinco años. Fueron tratadas entre 2006 y 2017, y estabilizadas con un clavo cefalomedular. Este grupo fue comparado con un grupo de control de similares características. Resultados: Veintidós tenían fracturas subtrocantéricas y 12, diafisarias. El 14% de las que tomaron bifosfonatos y fueron operadas requirió una revisión frente al 5,5% del grupo de control. El tiempo promedio de consolidación fue mayor en las tratadas con bifosfonatos (8.5 vs. 6 meses), con una diferencia estadísticamente significativa (p <0,001). Conclusiones: El beneficio del tratamiento con bifosfonatos en la prevención de fracturas es superior al riesgo de fracturas atípicas; sin embargo, es importante evaluar la relación riesgo-beneficio en cada paciente al comienzo y durante el tratamiento, teniendo en cuenta que, pese a esto, el tiempo de curación es más largo. Nivel de Evidencia: IV
Objectives: Bisphosphonates have become the gold standard treatment for osteoporosis, since they reduce the incidence of fractures. Recently, several papers described the occurrence of low-energy atypical femoral fractures associated with the use of bisphosphonates. The objective of this study was to compare the average time to healing of atypical femoral fractures in patients who received bisphosphonates and in a control group. Materials and Methods: We retrospectively evaluated 34 patients with atypical femoral fractures, 16 of whom had received treatment with bisphosphonates for at least 5 years, between 2006 and 2017, and whose fractures were stabilized with a cephalomedullary nail. They were compared with a control group of similar characteristics. Results: All the patients were female, with an average age of 74 years. Twenty-two fractures were subtrochanteric, while 12 involved the femoral shaft. Fourteen percent (14%) of the patients who received bisphosphonates and surgical management required a revision surgery, while 5.5% of the control group did not. The average time to bone healing was longer in those treated with bisphosphonates (8.5 months vs. 6 months), which was statistically significant (p <0.001). Conclusions: The benefits of using bisphosphonates for fracture prevention outweigh the risk of atypical fractures. However, it is important to evaluate the risk-benefit ratio in each patient at the beginning of the treatment and during the course of it, since, despite the benefits, healing time is longer. Level of Evidence: IV
Тема - темы
Aged , Osteoporosis , Diphosphonates/therapeutic use , Femoral Fractures , Incidence , Treatment OutcomeРеферат
La osteopenia, una disminución de la densidad mineral ósea de menor severidad que la osteoporosis, definida por valores de T-score entre -1,0 y -2,5 en la densitometría ósea , podría asociarse con un mayor riesgo de fracturas. Motivado por el pedido de una paciente con osteopenia que solicita a su médico algún medicamento que le ayude a disminuir su riesgo de fracturas, el autor se pregunta si los bifosfonatos podrían ser beneficiosos para las pacientes con este factor de riesgo. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, se concluye que estos fármacos podrían ser útiles para prevenir fracturas en mujeres mayores de 65 años con elevado riesgo de fractura,independientemente del resultado de la densitometría. (AU)
Osteopenia, a minor decrease in bone mineral density, defined by T-score values between -1.0 and -2.5 in a bone densitometry, is associated with an increased risk of fractures. Moved by the request of a patient with osteopenia who asks her doctor for any medication that may help her reduce his risk of fractures, the author wonders if bisphosphonates could be beneficial for patients with this condition. After conducting a bibliographic search and selecting the most recent and best quality evidence, he concluded that these drugs could be useful to prevent fractures in women older than 65 years with ahigh risk of fracture, regardless of densitometry results. (AU)
Тема - темы
Humans , Female , Aged , Osteoporosis/drug therapy , Bone Diseases, Metabolic/drug therapy , Diphosphonates/therapeutic use , Osteoporotic Fractures/prevention & control , Osteoporosis/etiology , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/diagnostic imaging , Risk Factors , Osteoporotic Fractures/physiopathology , Osteoporotic Fractures/drug therapyРеферат
El propósito de la terapia en el desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica (IRC) consiste en restaurar el balance mineral, y, en la osteoporosis, mantener o aumentar la masa ósea. Ambas terapias tratan de evitar la fractura ósea. La mayoría de los osteoactivos están contraindicados en la insuficiencia renal crónica avanzada (estadios 4 y 5), y las terapias son empíricas. Algunos autores opinan que sin anomalías bioquímicas del desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica avanzada se podría intentar el tratamiento estándar para la osteoporosis. Antes de intentar la terapia osteoactiva se debe corregir el desorden mineral óseo que pudiera presentarse asociado a la IRC, y en la indicación del tipo de osteoactivo se sugiere seleccionar al paciente según su estado óseo. Se aconseja que la administración de los antirresortivos se realice a dosis menores con respecto a los que tienen mejor función renal junto con aportes adecuados de calcio y vitamina D, antes y durante el tratamiento para prevenir el riesgo de severas hipocalcemias y un efecto óseo excesivo. Se presenta el caso clínico de una mujer de 65 años, con diagnóstico de osteoporosis de etiología multifactorial, fractura de pelvis, múltiples fracturas vertebrales e insuficiencia renal crónica avanzada, entre otras comorbilidades, y probable enfermedad ósea adinámica. Recibió inicialmente terapia con teriparatide y luego con denosumab, complicándose con hipocalcemia asintomática. (AU)
The purpose of therapy for the bone mineral metabolism disorder associated with chronic kidney disease is to restore the mineral balance; and to maintain or increase bone mass in osteoporosis. The goal of both types of therapy is to avoid bone fractures. Most antiosteoporotic drugs are contraindicated in advanced chronic renal failure (CRF) stages 4 and 5, and the therapies are empirical. Some authors believe that without biochemical abnormalities of the mineral bone metabolism disorder associated with advanced chronic kidney disease, standard treatment for osteoporosis could be attempted. Before attempting antiosteoporotic therapy, the bone mineral disorder that may be associated with CRF must be corrected, and in the indication of the type drug it is suggested that the patient be selected according to their bone status. It is advised that the administration of anti-resorptives be performed at lower doses in individuals with poor renal function compared to those with better renal function together with adequate calcium and vitamin D, before and during treatment to prevent the risk of severe hypocalcemia, and an excessive bone effect. We present the clinical case of a 65-year-old woman with a diagnosis of osteoporosis of multifactorial etiology, pelvic fracture, multiple vertebral fractures and advanced chronic renal failure, among other comorbidities and probable adynamic bone disease. The patient received initial therapy with teriparatide and followed by denosumab administration and exhibited asymptomatic hypocalcemia. (AU)
Тема - темы
Humans , Female , Aged , Chronic Kidney Disease-Mineral and Bone Disorder/drug therapy , Fractures, Bone/prevention & control , Osteoporosis/therapy , Chronic Kidney Disease-Mineral and Bone Disorder/complications , Chronic Kidney Disease-Mineral and Bone Disorder/metabolism , Chronic Kidney Disease-Mineral and Bone Disorder/therapy , Vitamin D/administration & dosage , Vitamin D/therapeutic use , Calcium/administration & dosage , Calcium/therapeutic use , Alendronate/therapeutic use , Teriparatide/administration & dosage , Teriparatide/adverse effects , Teriparatide/therapeutic use , Diphosphonates/administration & dosage , Diphosphonates/adverse effects , Diphosphonates/therapeutic use , Cinacalcet/therapeutic use , Risedronic Acid/therapeutic use , Denosumab/administration & dosage , Denosumab/adverse effects , Denosumab/therapeutic use , Hypocalcemia/prevention & controlРеферат
CONTEXTO: La osteoporosis es un trastorno esquelético caracterizado por resistencia óssea comprometida, predisposición pacientes a un mayor riesgo de fractura. La prevalência aumenta del 6% de las mujeres de edad 50 a 59 años a más del 40% de las mujeres de edad 80 años y mayores.1 Consecuencias de mantener una fractura puede ser grave e incluir un aumento riesgo de fracturas posteriores, hospitalización o institucionalización, disminución de la calidad de vida, y mortalidad prematura, con una carga relacionada com el sistema de salud. DESCRIPCIÓN DE LA TECNOLOGÍA: El denosumab es un anticuerpo monoclonal que inhibe la resorción ósea producida por los osteoclastos. Fue comercializado en 2010 para el tratamiento de la osteoporosis. En estos años se han identificado varios efectos adversos potencialmente graves: predisposición a infecciones, cáncer, reacciones de hipersensibilidad, transtornos autoinmunes, e incremento de la incidencia de múltiples fracturas vertebrales espontáneas al suspender el tratamiento. En este número revisamos estas novedades. TECNOLOGÍAS ALTERNATIVAS: Los agentes antirresortivos como los bifosfonatos orales son el estándar tratamiento para la osteoporosis posmenopáusica, en conjunto con medidas no farmacológicas y sobre todo el énfasis en la prevención de las caídas. Otras opciones de tratamiento incluyen un bisfosfonatos intravenoso (ácido zoledrónico), un agente formador de hueso (teriparatida) y un modulador selectivo del receptor de estrógeno (raloxifeno). MÉTODOS: Se realizó una búsqueda bibliográfica utilizando las siguientes bases de datos bibliográficas: MEDLINE, EMBASE, The Cochrane Library, y PubMed. Aplicaron filtros metodológicos para evaluaciones de tecnología sanitaria, estudios económicos, revisiones sistemáticas, metanálisis, y ensayos controlados aleatorios (ECA). La búsqueda también se limitó a Idioma en Inglés y humanos. Se excluyeron los resúmenes de congresos en los resultados de búsqueda. Se identificó la literatura gris (literatura que no se publica comercialmente) fue identificado mediante la búsqueda de secciones relevantes de la Lista de verificación de Grey Matters (http://www.cadth.ca/en/resources/grey-matters). Google y otros motores de búsqueda de internet fueron se utiliza para buscar en la web adicional materiales Estas búsquedas se complementaron con revisar las bibliografías de documentos clave y a través de contactos con expertos apropiados. ESTRATEGIA DE BÚSQUEDA: Se realizó una búsqueda con última fecha 26/08/2019 en diversas bases de datos, incluidas PubMed y Embase, así como la biblioteca Cochrane, ClinicalTrials.gov y bases de datos de revisiones sistematicas Epistemonikos. La búsqueda sólo incluyó documentos escrito en ingles y espanol. RESULTADOS: Denosumab comparado con placebo para pacientes con osteoporosis. El riesgo en el grupo de intervención (y su intervalo de confianza del 95%) se basa en el riesgo asumido en el grupo de comparación y en el efecto relativo de la intervención (y su intervalo de confianza del 95%). Eficacia frente a bifosfonatos: comparaciones directas. Se evalúa el perfil de evidencia GRADE donde se evidencia el metaanálisis entre cuatro ECA 5-8 que comprendieron 2071 participantes con un rango de seguimiento de 12 a 24 meses y compararon el uso de Denosumab con bifosfonatos orales (Alendronato,Etidronato). Existe incertidumbre en el efecto de denosumab sobre el riesgo de fracturas en comparación con bifosfonatos. La certeza em la evidencia va desde BAJA A MUY BAJA considerando la presencia de imprecisión muy seria y el potencial riesgo de sesgo de publicación. Eficacia frente a bifosfonatos: comparaciones indirectas. No se han encontrado en la literatura comparaciones directas entre Denosumab y otros fármacos distintos. Esta recomendación de cobertura otorga más peso a la incertidumbre en la eficacia comparada con bifosfonatos, al potencial impacto presupuestario de su uso y la potencial reducción de la equidad; que a la preferencia de los pacientes respecto de la forma de administración de las drogas para osteoporosis.
Тема - темы
Humans , Female , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/therapeutic use , Raloxifene Hydrochloride/therapeutic use , Diphosphonates/therapeutic use , Osteoporotic Fractures/drug therapy , Denosumab/therapeutic use , Zoledronic Acid/therapeutic use , Technology Assessment, Biomedical , Cost-Benefit Analysis/economicsТема - темы
Humans , Male , Female , Diphosphonates/administration & dosage , Fractures, Bone/prevention & control , Denosumab/administration & dosage , Osteoporosis/drug therapy , Risk Factors , Alendronate/administration & dosage , Alendronate/therapeutic use , Diphosphonates/therapeutic use , Denosumab/therapeutic use , Zoledronic Acid/administration & dosageРеферат
Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)
The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)
Тема - темы
Humans , Female , Middle Aged , Aged , Spinal Fractures/drug therapy , Denosumab/adverse effects , Osteoporosis/drug therapy , Quality of Life , Menopause , Biomarkers , Bone Density/drug effects , Calcium/administration & dosage , Spinal Fractures/prevention & control , Charybdotoxin/analysis , Calcium Citrate/administration & dosage , Alendronate/administration & dosage , MicroRNAs/metabolism , Diphosphonates/adverse effects , Diphosphonates/therapeutic use , RANK Ligand/drug effects , Denosumab/administration & dosage , Tobacco Smoking , Zoledronic Acid/administration & dosage , Ibandronic Acid/administration & dosage , Indapamide/administration & dosageРеферат
Resumen: Introducción: La osteogénesis imperfecta (OI) es un grupo heterogéneo de enfermedades hereditarias, las cuales cursan con la presencia de fragilidad ósea, fracturas frecuentes, deformidades óseas y talla baja. El tratamiento con bifosfonatos en los pacientes con diagnóstico de OI ha demostrado un decremento en la frecuencia de fracturas, así como una mejoría en la densidad ósea vertebral. Existe poca evidencia sobre la calidad de vida en pacientes con OI posterior al tratamiento con bifosfonatos. ¿Los bifosfonatos mejoran la calidad de vida de los pacientes con OI? Material y métodos: Se trata de un ensayo prospectivo, de intervención deliberada, ensayo clínico autocontrolado. Nueve pacientes que se encontraban entre las edades de dos y 13 años con diagnóstico de OI fueron tratados con ácido zolendrónico. Se realizó una medición de la calidad de vida en los pacientes previa y posteriormente. Para la medición de la calidad de vida de los pacientes utilizamos la encuesta de calidad de vida PedsQL 4.0 que fue aplicada tanto a los niños como a los padres. Resultados: En la encuesta de calidad de vida efectuada a los padres se observó un incremento en las cuatro dimensiones evaluadas. En la encuesta realizada a los niños se apreció un aumento en dos dimensiones. El número de fracturas disminuyó posterior al tratamiento. Conclusiones: Existe una correlación entre la disminución del número de fracturas y la percepción que tienen tanto los padres como los niños en la calidad de vida posterior al tratamiento con bifosfonatos.
Abstract: Introduction: Osteogenesis imperfeta (OI) is defined as a heterogeneous group of hereditary diseases, which present with the presence of bone fragility, frequent fractures, bone deformities and short stature. Treatment with biphosfonates in patients with diagnosis of OI has shown a decrease in the frecuency of fractures, as well as an improvement in vertebral bone density. There is little evidence on quality of life in patients diagnosed with OI treated with bisphosphonates, Therefore this study evaluated the quality of life of patients diagnosed with OI after treatment with bisphosphonates. Material and methods: It is a prospective, deliberate intervention, self-controlled clinical trial. Nine patients with ages between two and thirteen ages and diagnosed with OI were treated with Zolendronic, a quality of life measurement was performed in the patients before and after the application. For measuring the quality of life in the patients we used the PedsQL 4.0 quality of life survey that was applied to both children and parents. Results: In the quality of life survey performed on the parents, an increase was observed in the four dimensions evaluated. In the survey made on the children two dimensions showed a significant increase. The number of fractures decreased after the treatment. Conclusions: There is a correlation between the decrease in the number of fractures and the perception that both parents and children have in the quality of life after treatment with bisphosphonates.
Тема - темы
Humans , Child, Preschool , Child , Adolescent , Osteogenesis Imperfecta/complications , Osteogenesis Imperfecta/drug therapy , Quality of Life , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Prospective StudiesРеферат
Abstract The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Thirty Albinus Wistar male rats were administered 0.035 mg/kg zoledronic acid intravenously for 8 weeks, divided into four administrations with a 2-week interval between each application, after which their upper right central incisors were extracted to induce the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The samples were divided into the following two groups: Group 1 (G1) underwent marginal resection of BRONJ followed by the use of PRP, while Group 2 (G2) underwent resection of BRONJ but without the use of PRP. The treatment groups were evaluated after 14, 28, and 42 days. Clinical, microtomographic, microscopic, and immunohistochemical (IHC) evaluations were performed. Microtomography results revealed no significant difference between the groups (p <0.05) in any time period. Histomorphometric analysis showed increased bone formation over time for both groups (p < 0.001). G1 demonstrated a greater amount of new bone formation than G2 at 28 and 42 days (p < 0.001), with G1 presenting greater vascularization and a slightly higher VEGF expression. For both groups, RANKL/OPG expression levels were sufficient as a parameter for indicating the rate of bone remodeling in a previously treated area of osteonecrosis groups. Taken together, our findings indicated that the use of PRP improves the resolution process of BRONJ.
Тема - темы
Animals , Male , Rats , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Platelet-Rich Plasma , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Osteoclasts/drug effects , Tooth Extraction/adverse effects , Wound Healing , Rats, Wistar , Disease Models, Animal , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathologyРеферат
Statins are a widely prescribed class of medications that inhibit similar pathways as the anti-resorptive bisphosphonate drugs. Statins target the mevalonate pathway by blocking HMG-CoA reductase. Several recent meta-analyses concluded statins are osteoprotective in the general population. Here we present current literature exploring the mechanisms underlying the putative osteoprotective effects of statins. We also review recent clinical studies, ranging from observational cohort studies to randomized clinical trials, testing the effect of statins on bone health in various populations. (AU)
Las estatinas son un grupo de drogas prescriptas en forma habitual, con la capacidad de bloquear vías de señalización similares a las inhibidas por los amino-bisfosfonatos. Las estatinas inhiben la vía del mevalonato, a través del bloqueo de diferentes enzimas. Varios metaanálisis recientes llevaron a la conclusión de que las estatinas tienen capacidad osteoprotectora en la población general. En esta revisión presentamos la literatura actual describiendo los mecanismos que subyacen en el potencial efecto osteoprotector de las estatinas, como así también estudios observacionales y clínicos aleatorizados sobre el efecto de estatinas en la salud ósea en diversas poblaciones. (AU)
Тема - темы
Humans , Animals , Male , Female , Middle Aged , Aged , Aged, 80 and over , Mice , Osteoporosis/prevention & control , Bone Density/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Osteoblasts/drug effects , Osteoclasts/drug effects , Osteoporosis/drug therapy , Bone and Bones/metabolism , Postmenopause/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , GTP-Binding Proteins/drug effects , Simvastatin/administration & dosage , Diphosphonates/therapeutic use , Diphosphonates/pharmacology , Dyslipidemias/drug therapy , Fractures, Bone/prevention & control , Atorvastatin/administration & dosage , Mevalonic Acid/pharmacologyРеферат
SUMMARY Hypercalcemia can be hazardous during pregnancy, most cases being due to primary hyperparathyroidism. We report a case of hypercalcemia with suppressed PTH levels necessitating treatment with bisphosphonates during pregnancy. A 38-year-old woman at the 26th week gestation was admitted because of symptomatic hypercalcemia. She did not take any medication that could influence her calcium levels. Physical examination was unremarkable. Laboratory tests on admission were: calcium 12.7 mg/dL (8.5-10.5 mg/dL), phosphorus 1.8 mg/dL (2.5-4.5 mg/dL) and PTH on 3 consecutive tests 1.2, 1.3 and 1.2 pg/mL (15-65 pg/mL). Her 24h urine calcium was 900 mg, 25-OH-D 40 ng/mL (30-58 ng/mL) and 1,25-OH-D 99 pg/mL (80-146 for women in the third trimester). Abdominal ultrasound revealed multiple hypervascular liver lesions consistent with hemangiomas by MRI. Breast and neck ultrasound were normal, and chest CT revealed few non-significant 0.3-0.7 cm pulmonary nodules with no change after an interval of 3 months. She was treated with isotonic saline, loop diuretics and calcitonin. Despite this treatment, calcium levels remained high (14.1 mg/dL), and pamidronate was initiated. On 35th week gestation, she underwent a cesarean section complicated by hypocalcemia of the newborn. Eight weeks after delivery, her calcium levels are 9.4 mg/dL and PTH 18 mg/dL. According to the extensive workup and the post-partum normalization of PTH and calcium levels, we conclude that excessive secretion of placental PTHrP was the cause of hypercalcemia in this patient. No significant adverse effect of bisphosphonate on the mother or baby were seen at the short term follow up.