Fracturas vertebrales múltiples postsuspensión de denosumab: revisión del tema a partir de dos casos clínicos / Discontinuation of denosumab and multiple vertebral fractures: report of two cases and review of the literature

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)

Cascada de fracturas vertebrales en paciente osteoporótica al año de suspender Denosumab / Cascade of vertebral fractures in osteoporotic patient one year after Denosumab

Una paciente con osteoporosis había sido tratada por 4 años con ibandronato oral, luego por 1 año con ranelato de estroncio, y finalmente por 4 años con denosumab. En vista de la buena respuesta densitométrica este fármaco fue suspendido a fines de 2015. A los 14 meses la enferma tuvo lumbalgia aguda y se detectó hundimiento del platillo superior de L1, a lo que siguieron en rápida sucesión iguales lesiones en L2 y L3, y acuñamiento de D11 y D12. Se descartaron causas de osteoporosis secundaria. El plan terapéutico incluye corsé ortopédico, analgésicos, y teriparatida. En los dos últimos años se han publicado varios casos de este síndrome.

A patient with osteoporosis had been treated for 4 years with oral ibandronate, then for 1 year with strontium ranelate, and finally for 4 years with denosumab. In view of the good densitometric response to the latter, the drug was discontinued in December 2015. Fourteen months later the patient had acute low back pain; crushing of the upper plate of L1 was detected, followed by similar lesions in L2 and L3, and wedging of D11 and D12. Causes of secondary osteoporosis were ruled out. The therapeutic strategy includes a corset, analgesics, and teriparatide. In the last two years several cases of this syndrome have been reported.

Osteoporosis y osteosíntesis / Osteoporosis and osteosynthesis

Introducción: las manifestaciones clínicas de las osteoporosis incluyen las fracturas debido a pérdida de masa ósea y cambios estructurales en las trabéculas. En estos casos la osteosíntesis se ve afectada por los factores mecánicos inherentes al proceder y los implantes. Objetivo: mostrar las precauciones que el ortopédico necesita tener en mente al seleccionar el tipo de osteosíntesis (interna o externa) y los implantes que vaya a utilizar. Métodos: se realizó una revisión de las distintas precauciones en cirugía ortopédica sobre fracturas vertebrales y de huesos largos, así como su osteosíntesis de acuerdo a instrumental, implante y proceder operatorio. Resultados: se enfatiza en los avances incorporados, en especial, los sistemas mínimo invasivos de estabilización ósea, el uso de implantes con cerrojos"y el recubrimiento de clavos con hidroxiapatita de calcio y alambres para fijación externa. Conclusión: la osteosíntesis precoz, definitiva y eficaz, es el tratamiento de elección en las fracturas poróticas

Introduction: the clinical manifestations of osteoporosis include fractures due to a loss of bone mass and structural changes in trabeculae. In these cases the osteosynthesis is affected by the mechanical factors inherent to procedure and to implants. Objective: to show the cautions that orthopedist must to take into account at selecting the type of osteosynthesis (internal or external) and the implants to be used. Methods: a review of the different cautions in orthopedic surgery on vertebral fractures and long bones was carried out as well as its osteosynthesis according to the instrumental, the implant and operative procedure. Results: it is emphasize on the incorporated advances, specially the minimally invasive systems of bone stabilization, the use of implants with bolts and nails covering or coating with calcium hydroxyapatite and wires for external fixation. Conclusion: the early, definitive and effective osteosynthesis is the choice treatment in porous fractures

Ranelato de estroncio: tratamiento para osteoporosis: [revisión] / Strontium ranelate in the treatment of osteoporosis: [review]

El estroncio es un catión divalente que incrementa la formación ósea y disminuye la resorción.Este mecanismo de acción dual, disociando el remodelado, puede explicarse por su acción anivel del receptor sensor de calcio de osteoblastos, estimulando la diferenciación y actividad deosteoblastos e inhibiendo diferenciación y la acción de osteoclastos vía receptor RANK-L (ligandodel receptor del activador nuclear del factor kB). Es efectivo para reducir las fracturas vertebralesy no vertebrales en pacientes menopáusicas. Disminuye la incidencia de fracturas de cadera enpacientes >74 años con factores de riesgo adicionales. Se ha demostrado persistencia de suacción luego de 8 años de tratamiento. La acumulación de estroncio en el tejido óseo es progresivahasta alcanzar un máximo al tercer año de tratamiento. La eliminación del mismo, al terminar laterapia, puede inferirse por el cambio de los marcadores bioquímicos al tercer mes de suspendido,sugiriendo que la droga es eliminada rápidamente. Se administra en forma de suspensión oral,tiene buena tolerancia y los efectos adversos son leves, similares al placebo.Es una buena opción para el tratamiento de osteoporosis.

The use of PTH in the treatment of osteoporosis / Uso do PTH no tratamento da osteoporose

Anabolic drugs have recently widened therapeutic options in osteoporosis treatment, as they influence processes associated with bone formation to a greater extent and earlier than bone reabsortion. They positively affect a number of skeletal properties besides bone density, as intermittent administration of parathyroid hormone (PTH) results in an increase in the number and activity of osteoblasts leading to an increase in bone mass and improvement in skeletal architecture at both the trabecular and cortical bone. Human recombinant parathyroid hormone (hrPTH 1-84) and human recombinant PTH peptide 1-34 (teriparatide) belong to this group. The objective of this paper is to review PTH actions, benefits and adverse effects, action on biochemical markers, combination therapy with antiresorptive agents, impact of antiresorptive therapy prior to anabolic treatment, sequential treatment, and effect on glucocorticoid-induced osteoporosis.

As drogas anabólicas ampliaram recentemente as opções terapêuticas no tratamento da osteo-porose e influenciam em maior escala os processos relacionados com a formação óssea, que ocorrem antes do efeito na reabsorção. Essas drogas afetam um grande número de propriedades esqueléticas, além da densidade mineral óssea. A administração intermitente de PTH leva a um aumento do número e atividade dos osteoblastos, ocasionando aumento da massa óssea e melhora da arquitetura, tanto do osso trabecular quanto cortical. O paratormônio recombinante humano (hrPTH 1-84) e o peptídeo recombinante humano 1-34 (teriparatide) pertencem a esse grupo de agentes. O objetivo deste artigo é revisar as ações, os benefícios e os efeitos adversos do PTH, assim como sua ação nos marcadores bioquímicos do metabolismo ósseo, a terapia combinada com drogas antirreabsortivas, o impacto do uso dos antirreabsortivos antes do tratamento anabólico, o tratamento sequencial e o tratamento da osteoporose induzida por glicocorticoides.

Fracturas vertebrales osteoporóticas: manejo conservador / Osteoporotic vertebral fractures: conservative management

Osteoporotic vertebral fractures are a consequence of a systemic skeletall disease (osteoporosis) that results in an increase of bone fragility and fracture risk. The Orthopedic Surgeon may be the only doctor who evaluate a patient with a fracture and should be able to show whether this is due to osteoporotic process, to give an integral treatment and prevent future fractures. Vertebral osteoporotic fracture, are associated with pain, disability, increased morbidity and mortality and a major economic impact on society. Conservative treatment of these fractures is composed of non-pharmacological and pharmacological treatment. The nonpharmacological treatment serves as a complement to pharmacological treatment and optimizes the reduction in risk of fractures. The main objective of treatment is to prevent future fractures. The secondary objectives are to reduce pain and disability associated. In this review of the literature, we summarize the drugs and techniques currently used to treat osteoporosis and to prevent future fractures.

Las fracturas vertebrales osteoporóticas son parte de una enfermedad esquelética sistémica (osteoporosis) que resulta en un aumento de la fragilidad ósea y del riesgo a fracturarse. El traumatólogo puede ser el único médico que evalúe a un paciente con una fractura y debe ser capaz de demostrar si esta es de causa osteoporótica, para así dar un tratamiento integral y prevenir fracturas futuras. Las fracturas vertebrales osteoporóticas (FVO) se asocian a dolor, discapacidad, aumento de morbi-mortalidad y un gran impacto económico para la sociedad. El tratamiento de estas fracturas tiene un manejo farmacológico y no farmacológico. El tratamiento no farmacológico complementa el tratamiento farmacológico y optimiza la reducción del riesgo de fracturas. El principal objetivo del tratamiento es el de prevenir nuevas fracturas. Los objetivos secundarios son disminuir el dolor y la discapacidad asociada. En esta revisión de la literatura se señalaran los fármacos y técnicas utilizadas en la actualidad para el tratamiento de la osteoporosis y prevención de nuevas fracturas.

Glucocorticoid-induced osteoporosis / Osteoporose induzida por glicocorticóide

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.

A osteoporose induzida por glicocorticóides é a causa mais freqüente de osteoporose secundária. Os glicocorticóides causam uma perda óssea rápida nos primeiros meses de uso da medicação; entretanto, o seu efeito mais importante é uma supressão significativa da formação óssea. A administração oral de glicocorticóides está associada a um aumento no risco de fraturas na coluna e no quadril. O risco é dose dependente; entretanto, mesmo doses baixas de glicocorticóides podem aumentar o risco de fraturas. Os pacientes em uso de glicocorticóides perdem mais osso trabecular que osso cortical; em conseqüência, as fraturas são mais freqüentes na coluna que no quadril. O uso concomitante de cálcio e vitamina D ou formas ativas da vitamina D previne a perda óssea, e as drogas anti-reabsortivas são efetivas na prevenção e tratamento da perda óssea e diminuem o risco de fraturas. Apesar de os efeitos deletérios dos glicocorticóides sobre o osso serem bastante conhecidos, poucos pacientes são orientados ou recebem tratamento preventivo associado à terapia com glicocorticóides.

Comparison of Effect of Treatment with Etidronate and Alendronate on Lumbar Bone Mineral Density in Elderly Women with Osteoporosis

The purpose of this open-labeled prospective study was to compare the treatment effects of cyclical etidronate and alendronate on the lumbar bone mineral density (BMD), bone resorption, and back pain in elderly women with osteoporosis. Fifty postmenopausal women with osteoporosis, age ranging from 55 to 86 years (mean: 70.7 years), were randomly divided into two groups with 25 patients in each group: the cyclical etidronate group (etidronate 200 mg daily for 2 weeks every 3 months) and the alendronate group (5 mg daily). The BMD of the lumbar spine (L1-L4) measured by DXA, the urinary cross-linked N-terminal telopeptides of type I collagen (NTX) level measured by the enzyme-linked immunosorbent assay, and back pain evaluated by the face scale score were assessed at baseline, 6 months, and 12 months. There were no significant differences in baseline characteristics including age, body mass index, years since menopause, lumbar BMD, urinary NTX level, and face scale score between the two treatment groups. Etidronate treatment sustained the lumbar BMD following a reduction in the urinary NTX level and improved back pain, while alendronate treatment reduced the urinary NTX level more significantly, resulting in an increase in the lumbar BMD, and similarly improved back pain. No serious adverse events were observed in either group. This study confirmed that alendronate treatment had a greater efficacy than etidronate treatment in increasing the lumbar BMD through the reduction of bone resorption in elderly women with osteoporosis.