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1.
Bone Joint J ; 102-B(2): 177-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009426

RESUMO

AIMS: To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). METHODS: This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). RESULTS: There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. CONCLUSION: Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177-185.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/cirurgia , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/cirurgia , Sacro/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/tratamento farmacológico , Criança , Terapia Combinada , Curetagem/métodos , Feminino , Tumor de Células Gigantes do Osso/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
2.
Medicine (Baltimore) ; 98(47): e18067, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764838

RESUMO

Osteoporosis is a complication of type 2 diabetes mellitus (T2DM). Blockade of receptor activator of nuclear factor kappa-B ligand (RANKL) improves osteoporosis, but might also improve glucose tolerance through reduction of hepatic insulin resistance. However, the effect of denosumab (a human monoclonal antibody of RANKL) upon glycemic and metabolic parameters is controversial. We revealed the effect of denosumab upon glycemic and metabolic parameters for 52 weeks. We evaluated 20 individuals diagnosed with both osteoporosis (male and female: postmenopausal) and T2DM. We measured glycemic and metabolic parameters before and 26/52 weeks after administration of denosumab (60 mg per 26 weeks) without changing any other medication each patient was taking. All patients completed the study without complications and the T-score (lumbar spine and femoral neck) improved significantly from baseline to 52 weeks after denosumab administration (P < .001, .001, respectively). None of the glycemic parameters changed significantly from baseline to 26 weeks after denosumab administration, but levels of glycated hemoglobin and homeostasis model assessment of insulin resistance improved significantly from baseline to 52 weeks after administration (P = .019, .008, respectively). The levels of liver enzymes did not change significantly from baseline to 26 weeks after denosumab administration, but levels of aspartate transaminase and alanine aminotransferase improved significantly from baseline to 52 weeks after administration (P = .014, .004, respectively). None of the markers of lipid metabolism and body mass index changed significantly from baseline to 26/52 weeks after denosumab administration. These data demonstrated that denosumab is useful for T2DM patients with osteoporosis for glycemic control via improvement of insulin resistance. Also, the effect of denosumab might be due to improvement of hepatic function.


Assuntos
Glicemia/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/farmacologia , Denosumab/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Osteoporose/metabolismo , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Osteoporose/etiologia , Ligante RANK/imunologia
3.
Bone Joint J ; 101-B(11): 1402-1407, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31674239

RESUMO

AIMS: Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. PATIENTS AND METHODS: The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants' discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. RESULTS: Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. CONCLUSION: These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402-1407.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas do Quadril/cirurgia , Idoso , Cálcio/uso terapêutico , Estudos de Coortes , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Hidroxicolecalciferóis/uso terapêutico , Adesão à Medicação , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Teriparatida/uso terapêutico , Reino Unido , Vitamina D/uso terapêutico
4.
Medicine (Baltimore) ; 98(46): e17778, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725619

RESUMO

INTRODUCTION: Giant cell tumor of bone with pulmonary and bone metastases is exceedingly rare in adolescents. Furthermore, Denosumab and Sunitinib in the treatment of giant cell tumor of bone has never been reported. PATIENT CONCERNS: A 16-year-old boy complained of fever, chest tightness, and shortness of breath and back pain for 5 days. DIAGNOSIS: Giant cell tumor of bone with pulmonary and bone metastases. INTERVENTIONS: The patient underwent 2 surgeries for giant cell tumor of bone located in the spine and received Denosumab to reduce local recurrence and control the metastases. Then Sunitinib was added into treatment strategies after the progressing of metastases. OUTCOMES: Within 5 months of Denosumab and Sunitinib, lung metastases were shrinking (stable disease, response evaluation criteria in solid tumors version 1.1). Until now about 4 years into treatment the patient is still survival. Pulmonary and bone metastases are stable. CONCLUSIONS: This is a case of multi-center giant cell tumor of bone, it does not only provide a reference to the treatment of similar cases of the clinic but also reflects the limitations of the application of Denosumab in the real world.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Neoplasias da Coluna Vertebral/tratamento farmacológico , Sunitinibe/uso terapêutico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/secundário , Denosumab/administração & dosagem , Tumor de Células Gigantes do Osso/patologia , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Neoplasias Pulmonares/secundário , Masculino , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Sunitinibe/administração & dosagem
6.
Clin Interv Aging ; 14: 1445-1450, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496671

RESUMO

Discontinuation of denosumab during osteoporosis treatment leads to rapid loss of bone mineral density and induces a bone turnover rebound effect. Previous studies have reported analysis based on dual-energy X-ray absorptiometry scanning (DXA). Here, we report the first case involving analysis of three-dimensional bone mineral density and bone strength, measured by quantitative computed tomography (QCT) after discontinuation of denosumab. An 82-year-old woman who discontinued denosumab because of patient's wish was administered the fifth dose after a gap of 14 months. Her bone mineral density evaluated by DXA and QCT, bone strength, and bone turnover marker levels showed significant rebound phenomenon. The levels of the cortical parameters of the hip were also decreased indicating an increased risk of femoral fractures after denosumab interruption. Our case highlights the increased risk of fractures after discontinuation of denosumab. Therefore, denosumab must be used judiciously without interruption in the dosage schedule.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Suspensão de Tratamento , Absorciometria de Fóton , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Tomografia Computadorizada por Raios X
7.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373465

RESUMO

Osteoporosis affects a segment of the population in which Chronic Kidney Disease is also greatly represented. Nephropathic patients may present peculiar biochemical abnormalities related to Chronic Kidney Disease, defining the Mineral and Bone Disorder. This kind of anomalies, in the worst scenarios, configure the typical histomorphology patterns of Renal Osteodystrophy. Scientific Societies of Endocrinology have established therapy guidelines for patients with osteoporosis only based on the glomerular filtration rate and recommend avoiding the use of some drugs for the more advanced classes of nephropathy. However, there is no clear therapeutic approach for patients with advanced nephropathy and bone abnormalities. In this paper we propose a systematic review of the literature and present our proposal for managing patients with advanced nephropathy, based on eGFR and on presence of Mineral and Bone Disorder.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Anticorpos Monoclonais/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/química , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Contraindicações , Denosumab/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/química , Feminino , Fraturas Espontâneas/tratamento farmacológico , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Taxa de Filtração Glomerular , Humanos , Masculino , Osteoporose/complicações , Osteoporose/diagnóstico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Guias de Prática Clínica como Assunto , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Teriparatida/uso terapêutico
8.
Actual. osteol ; 15(2): 94-102, mayo - ago. 2019. tab.
Artigo em Espanhol | LILACS | ID: biblio-1048478

RESUMO

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)


Assuntos
Humanos , Feminino , Idoso , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Fraturas Ósseas/prevenção & controle , Osteoporose/terapia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Vitamina D/administração & dosagem , Vitamina D/uso terapêutico , Cálcio/administração & dosagem , Cálcio/uso terapêutico , Alendronato/uso terapêutico , Teriparatida/administração & dosagem , Teriparatida/efeitos adversos , Teriparatida/uso terapêutico , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Cinacalcete/uso terapêutico , Ácido Risedrônico/uso terapêutico , Denosumab/administração & dosagem , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Hipocalcemia/prevenção & controle
10.
BMJ Case Rep ; 12(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340943

RESUMO

A 35-year-old man with juvenile idiopathic arthritis since childhood presented with bilateral atypical tibial fractures, followed by a later, single atypical fracture of the femur. The fractures were associated with 6 years of oral alendronate treatment immediately followed by subcutaneous denosumab therapy and later teriparatide therapy for osteoporosis. Atypical fractures are known to occur in the femur following bisphosphonate therapy; however, there are only a few documented cases of atypical fractures in the tibia. Our case highlights a rare but serious complication of a commonly prescribed antiresorptive agent. It also shows that teriparatide, while helpful in increasing bone mass, does not fully prevent the development of atypical fractures. Careful investigation should be considered in patients on long-term antiresorptive therapy presenting with bony tenderness to exclude an atypical fracture.


Assuntos
Alendronato/efeitos adversos , Denosumab/efeitos adversos , Fraturas Espontâneas/induzido quimicamente , Osteoporose/tratamento farmacológico , Teriparatida/efeitos adversos , Absorciometria de Fóton/métodos , Adulto , Alendronato/uso terapêutico , Densidade Óssea/fisiologia , Denosumab/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/diagnóstico por imagem , Seguimentos , Fraturas Espontâneas/diagnóstico por imagem , Humanos , Masculino , Osteoporose/diagnóstico por imagem , Medição de Risco , Teriparatida/uso terapêutico , Fraturas da Tíbia/induzido quimicamente , Fraturas da Tíbia/diagnóstico por imagem
11.
Gulf J Oncolog ; 1(30): 67-75, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31242985

RESUMO

Giant cell tumor of bone (GCTB) is a biologically benign osteolytic tumor that affects the metaphyseal/epiphyseal portions of bones. Histologically, GCTB is composed of osteoclast-like multinucleated giant cells that express receptor activator of nuclear factor kappa B (RANK), and neoplastic mesenchymal stromal cells that express RANK ligand (RANKL). The pathogenesis of GCTB is primarily attributable to the RANK-RANKL interaction, resulting in the activation of osteoclasts and the resultant osteolytic phenotype. Denosumab is a monoclonal antibody targeted against RANKL. In 2013, it was approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is inoperable, or initial surgery is expected to culminate in substantial morbidity. The aim of this study is to narratively review the current literature on the role of preoperative denosumab followed by surgery in the management of patients with GCTB. In brief, caution should be exercised in the interpretation of existing data on preoperative denosumab in the management of GCTB patients, owing to some critical limitations, for example, short follow-up and only a minority of patients have undergone intralesional surgery following denosumab therapy. All in all, administration of preoperative denosumab is associated with clinical, radiological, and histopathological therapeutic benefits. It is also associated with tolerability, safety, surgical downstaging and less morbid salvageable procedures. Preoperative denosumab does not seem to reduce the likelihood of local recurrence after intralesional therapy; a planned randomized phase III clinical trial (JCOG 1610) will holistically address this concern. Furthermore, more than ten cases of denosumab-related malignant transformation of GCTB have been reported in literature. Lastly, large-sized phase III randomized clinical trials with long-term follow-up data are warranted to withdraw concrete conclusions and recommendations.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/terapia , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/terapia , Cuidados Pré-Operatórios , Procedimentos Cirúrgicos Operatórios/métodos , Neoplasias Ósseas/patologia , Terapia Combinada , Gerenciamento Clínico , Tumor de Células Gigantes do Osso/patologia , Humanos , Prognóstico
12.
Cancer Immunol Immunother ; 68(7): 1187-1194, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31187176

RESUMO

BACKGROUND: PD-1 inhibition (PD-1i) is the standard of care in melanoma and other malignancies. In patients with bone metastases of solid tumors, the monoclonal antibody denosumab directed against RANKL is approved for the prevention of skeletal-related events. However, RANKL is not only relevant in osteoclastogenesis, but also has immunological effects. Hence, we aimed at investigating, whether the combination of PD-1i and denosumab produces synergistic effects in metastatic melanoma treatment. METHODS: We retrospectively collected and analyzed clinical data of metastatic melanoma patients with bone metastases, who received PD-1i and denosumab therapy. RESULTS: 29 patients were identified with a median age of 60.7 years: 20 were male and 9 were female. 20 patients (69%) were in stage IV M1c and 9 (31%) in stage IV M1d; 52% had an increased serum LDH. 24 patients (83%) received PD-1i as first-line therapy and five patients (17%) as second- or third-line therapy. 13 patients received the triple combination nivolumab, ipilimumab and denosumab (N + I+D), 16 patients received PD-1i and denosumab (PD-1i + D). Within a median follow-up time of 19.8 months, 17 patients progressed with a median time to progression of 6 months. The objective response rate was 54% in the N + I + D group and 50% in the PD-1i + D group. Recalcification of bone metastases was radiologically observed in 18 (62%) patients. No unexpected treatment-related adverse events emerged. CONCLUSIONS: The combination therapy of metastatic melanoma with PD-1i and denosumab was feasible without unexpected safety issues and showed a promising efficacy signal. Further investigation in prospective studies is needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Denosumab/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Denosumab/farmacologia , Feminino , Humanos , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Ligante RANK/antagonistas & inibidores , Ligante RANK/imunologia , Estudos Retrospectivos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
13.
Br J Oral Maxillofac Surg ; 57(7): 691-693, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230854

RESUMO

The management of giant cell granulomas is challenging, and aggressive lesions have a high tendency to recur after enucleation alone. Based on assumptions regarding cell type and receptors, multiple pharmacological adjuncts have been used to manage them. We describe the use of denosumab, which was successfully used as a single method of treatment, suggesting that it may be a viable alternative or adjunct to operation on giant cell granulomas of the jaws.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Granuloma de Células Gigantes/tratamento farmacológico , Neoplasias Mandibulares/tratamento farmacológico , Granuloma de Células Gigantes/patologia , Humanos , Mandíbula , Neoplasias Mandibulares/patologia , Recidiva , Resultado do Tratamento
14.
Rehabilitación (Madr., Ed. impr.) ; 53(2): 126-130, abr.-jun. 2019. ilus
Artigo em Espanhol | IBECS | ID: ibc-185469

RESUMO

El edema óseo idiopático se considera una entidad de fisiopatología no aclarada y origen multifactorial que afecta a personas de mediana edad; se caracteriza por dolor e impotencia funcional en extremidades inferiores asociados a hallazgos característicos en resonancia magnética: imágenes hipointensas en T1 e hiperintensas en T2 en las articulaciones afectadas. Presentamos 3 casos clínicos de varones (edad: 45-64), 2 en rodillas y uno en cadera. Inicio con dolor intenso (EVA ≥ 5), sin desencadenante claro e impotencia funcional con imágenes características en resonancia magnética. Tratamiento: vitamina D (20.000 UI/semana vía oral) y dosis única subcutánea de denosumab (60mg) (indicación fuera de ficha técnica), descarga de articulación afectada y ejercicios autoasistidos de mantenimiento de recorrido articular. Evolución favorable con resolución clínica y del edema óseo, sin complicaciones reseñables. El denosumab se muestra como una opción de tratamiento para la resolución clínico-radiológica del edema óseo idiopático y parece acortar la evolución natural del proceso


Idiopathic bone marrow oedema is considered an unclarified pathophysiological entity of multifactorial origin affecting middle-aged persons; it is characterised by pain and functional limitation of the lower extremities. Characteristic findings on magnetic resonance imaging are hypointense T1 and hyperintense T2 images in the affected joints. We present 3clinical cases of BMO in men (age: 45-64 years), involving 2knees and one hip. Onset occurred with intense pain (VAS ≥ 5), with no clear cause and functional limitation with characteristic images on magnetic resonance imaging. Treatment consisted of vitamin D 20,000 IU/week orally and a single subcutaneous dose of denosumab 60mg (off label use). The patients avoided weight bearing on affected joints and conducted self-assisted exercises to maintain range of movement. Outcome was favourable with clinical and bone oedema resolution, with no notable complications. This report demonstrates that denosumab is a treatment option for the clinical/radiological resolution of bone marrow oedema and seems to shorten the clinical course of the process


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Edema/diagnóstico , Osteíte/tratamento farmacológico , Denosumab/uso terapêutico , Modalidades de Fisioterapia , Osteíte/reabilitação , Tramadol/uso terapêutico , Acetaminofen/uso terapêutico
15.
Drugs Aging ; 36(7): 625-638, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31066015

RESUMO

In patients with osteoporosis and severely reduced bone mass and/or recurring fractures, antiresorptive therapy may not be the optimal first-line treatment. Two recent clinical trials comparing bone-forming treatment with antiresorptive therapy have demonstrated that bone-forming treatment is superior in reducing the fracture risk in patients with severe osteoporosis. All of the currently available bone-forming agents-teriparatide, abaloparatide, and romosozumab-increase bone mineral density (BMD) and reduce the fracture risk; however, the effect wears off with time and treatment is therefore only transient. Thus, a bone-forming therapy should be followed by antiresorptive treatment with a bisphosphonate or denosumab. The BMD response to bone-forming treatment is reduced in patients previously treated with antiresorptive drugs; however, based on the findings of the VERO trial, the anti-fracture efficacy of bone-forming treatment in comparison with antiresorptives seems to be preserved. This review provides an overview of the existing bone-forming therapies for osteoporosis including considerations of sequential and combination therapy.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Quimioterapia Combinada , Humanos , Osteogênese/efeitos dos fármacos , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Teriparatida/uso terapêutico
16.
Cancer Treat Rev ; 76: 57-67, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31136850

RESUMO

Patients with solid tumours are at risk of impaired bone health from metastases and cancer therapy-induced bone loss (CTIBL). We review medical management of bone health in patients with solid tumours over the past 30 years, from first-generation bisphosphonates to the receptor activator of nuclear factor κB ligand (RANKL)-targeted monoclonal antibody, denosumab. In the 1980s, first-generation bisphosphonates were shown to reduce the incidence of skeletal-related events (SREs) in patients with breast cancer. Subsequently, more potent second- and third-generation bisphosphonates were developed, particularly zoledronic acid (ZA). Head-to-head studies showed that ZA was significantly more effective than pamidronate for reducing SREs in patients with breast and castrate-resistant prostate cancer (CRPC), becoming the standard of care for more than a decade. The RANKL inhibitor denosumab was licensed in 2010, and head-to-head studies and integrated analyses confirmed its superiority to ZA for preventing SREs, particularly in breast cancer and CRPC. Bisphosphonates and denosumab have also been investigated for prevention of CTIBL in patients receiving hormonal therapy for breast and prostate cancer, and denosumab is licensed in this indication. Despite advances in management of bone health, several issues remain, notably the optimal time to initiate therapy, duration of therapy, and dosing frequency, and how to avoid toxicity, particularly with long-term treatment. In summary, introduction of ZA and denosumab has protected patients with bone metastasis from serious bone complications and improved their quality of life. Ongoing research will hopefully guide the optimal use of these agents to help maintain bone health in patients with solid tumours.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Animais , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Denosumab/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Ácido Zoledrônico/uso terapêutico
17.
Osteoporos Int ; 30(7): 1455-1464, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31011760

RESUMO

Persistence rates over 36 months with denosumab in patients diagnosed with osteoporosis in a real-world setting were examined, along with baseline patient characteristics predictive of persistence. This study represents the longest observational period with denosumab persistence and shows higher persistence rates when compared to bisphosphonates. INTRODUCTION: The study objective was to describe long-term persistence with denosumab among patients treated for osteoporosis in a real-world setting. We also sought to examine patient characteristics predictive of persistence. Lastly, this study attempted to place the results in context by conducting a literature review of published persistence data for denosumab. METHODS: This retrospective, non-interventional study analyzed 1158 patients from a specialty community private practice to assess patient persistence with denosumab in routine care. Persistence was defined as receiving seven denosumab injections, using an 8-week permissible gap, over 36 months. Non-persistent patients were further investigated retrospectively to identify reasons for discontinuation, when available. RESULTS: Demographic analysis showed a population of 1158 patients with mean age 68.4 years old and baseline T-score - 2.7; nearly half of which experienced a prior osteoporosis-related fracture. In a Kaplan-Meier survival analysis, 36-month persistence overall was 50.7%. Net persistence, as defined by receiving seven injections in the allowable time frame, was 64.2% of the cohort. In a multivariate analysis, prior vertebral fractures and recent osteoporosis therapy were associated with higher persistence; age greater than 75 years was associated with non-persistence. Reasons for discontinuation were available in 91.6% of non-persistent patients and categorized to include the ten most common explanations. CONCLUSION: This study to our knowledge represents the longest continuous observational period providing data on denosumab persistence in a real-world setting. The total persistence noted is quite robust when compared to bisphosphonates and is within the upper range of prior published studies of denosumab with shorter observation periods.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Denosumab/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Osteoporose/tratamento farmacológico , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Estudos Retrospectivos , Estados Unidos
18.
Rev Med Suisse ; 15(647): 824-830, 2019 Apr 17.
Artigo em Francês | MEDLINE | ID: mdl-30994985

RESUMO

Two types of bone diseases can be observed in patients with breast or prostate cancer: fragility fractures related to osteoporosis, and skeletal related events (SRE) complicating bone metastases. Aromatase inhibitors, ovarian function suppression and tamoxifen use in pre-menopausal women, and androgen deprivation therapy, induce a decrease of bone mineral density and an increase of the incidence of fractures, which can be prevented by inhibitors of bone resorption at low doses. In addition, adjuvant bisphosphonates may be associated with benefits on disease free survival, especially regarding bone recurrences, in postmenopausal women with non-metastatic breast cancer. In the presence of bone metastases, inhibitors of bone resorption at higher doses and frequencies prevent SRE.


Assuntos
Conservadores da Densidade Óssea , Neoplasias Ósseas , Neoplasias da Mama , Denosumab , Neoplasias da Próstata , Antagonistas de Androgênios/uso terapêutico , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Denosumab/uso terapêutico , Difosfonatos , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias da Próstata/tratamento farmacológico
19.
J Med Econ ; 22(8): 766-776, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30969797

RESUMO

Aim: The approved indication for denosumab (120 mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy. Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study ("20090482") in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included. Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1-3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69-94%, 84-96%, 79-96%, and 50-92% likely to be cost-effective vs ZA, respectively. Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data. Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Denosumab/uso terapêutico , Mieloma Múltiplo/complicações , Ácido Zoledrônico/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/economia , Análise Custo-Benefício , Denosumab/efeitos adversos , Denosumab/economia , Relação Dose-Resposta a Droga , Esquema de Medicação , Europa (Continente) , Gastos em Saúde , Humanos , Cadeias de Markov , Modelos Econômicos , Mieloma Múltiplo/mortalidade , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/economia
20.
Paediatr Drugs ; 21(2): 95-106, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30941653

RESUMO

Increasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investigated in phase III trials (denosumab, vosoritide, palovarotene). To offer a multi-disciplinary therapeutic approach, it is recommended that patients with rare skeletal disorders are treated and monitored in highly specialized centers. This guarantees the greatest safety for the individual patient and offers the possibility of collecting data to further improve treatment strategies for these rare conditions. Additionally, new therapeutic options could be achieved through increased awareness, not only in the field of pediatrics but also in prenatal and obstetric specialties. Presenting new therapeutic options might influence families in their decision of whether or not to terminate a pregnancy with a child with a skeletal disease.


Assuntos
Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Raras/tratamento farmacológico , Fosfatase Alcalina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Criança , Denosumab/uso terapêutico , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Mutação , Gravidez , Pirazóis/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Estilbenos/uso terapêutico
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