Quiste óseo aneurismático del atlas: Tratamiento con denosumab y reporte de caso / Aneurysmal bone cyst of the atlas: treatment with denosumab and case report

Presentamos un caso de quiste óseo aneurismático (QOA) de ubicación infrecuente y comportamiento agresivo en un paciente masculino de 28 años, en que la resección quirúrgica es controversial por el riesgo de iatrogenia y eventual recurrencia. El tratamiento con denosumab ha sido recientemente propuesto como una alternativa para el manejo de QOAs irresecables o recurrentes; sin embargo, la literatura disponible es escasa. Reportamos nuestra experiencia en un caso y analizamos la bibliografía disponible

We present a case of aneurysmal bone cyst (ABC) of infrequent location and aggressive behavior in a 28-year-old male patient, in which surgical resection is controversial due to the risk of iatrogenicity and eventual recurrence. Treatment with denosumab has been recently proposed as an alternative for the management of unresectable or recurrent ABCs; however, the available literature is sparse. We report our experience with one case and analyze the available literature

Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2 years were treated with Denosumab, 42% with 120 mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70 mg. To avoid ADRs 500 mg of calcium and 400 IU of vitamin D orally were used. Initial effective response was reported after 1-3 months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120 mg, 60 or 70 mg in patients < 45 or 50 kg for ≥ 12 months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy.

Etiopathogenesis of medication-related osteonecrosis of the jaws: a review.

This study compiles the main hypotheses involved in the etiopathogenesis of medication-related osteonecrosis of the jaw (MRONJ). A narrative review of the literature was performed. The etiopathogenesis of MRONJ is multifactorial and not fully understood. The main hypothesis considers the disturbance of bone turnover caused by anti-resorptive drugs. Bisphosphonates and denosumab inhibit osteoclast activity through different action mechanisms, accumulating bone microfracture. Other hypotheses also consider oral infection and inflammation, the antiangiogenic effect and soft tissue toxicity of bisphosphonates, and the inhibition of lymphangiogenesis. Knowledge of the current theories for MRONJ is necessary to define future studies and protocols to minimize the incidence of this severe condition.

Twenty-four months of follow-up in women with rebound-associated vertebral fractures after discontinuation of denosumab: a single-centre case series.

Evidence on the management of rebound-associated vertebral fractures after denosumab discontinuation is scarce. This study describes seven patients retreated with denosumab, teriparatide or zoledronate for 24 months. Their bone mineral density remained stable or improved and no new fractures occurred suggesting that all three options might be adequate for their treatment. PURPOSE: To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24 months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. METHODS: Patients with RAVFs who received retreatment (RT) for 24 months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24 months. RESULTS: Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24 months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24 months of follow-up, no patient suffered new fractures. CONCLUSION: In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24 months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options.

Pérdida de stock óseo no osteoporótico en la columna. Denosumab como herramienta de tratamiento e implicancia / Non-osteoporotic loss of spinal bone. Denosumab as a therapeutic tool and its implications

Introducción: El denosumab es un anticuerpo monoclonal humano que actúa contra el RANKL, inhibiendo la destrucción ósea mediada por los osteoclastos, así evitando la pérdida de stock óseo; por este motivo, se lo utiliza en el tratamiento de la osteoporosis como agente antiresortivo y está autorizado para el tratamiento del tumor de células gigantes y el mieloma múltiple. Nuestro objetivo fue conocer las indicaciones y contraindicaciones para la pérdida de stock óseo de causa no osteoporótica. Materiales y métodos: Revisión sistemática de artículos en inglés publicados en el período 2009-2023. Se incluyeron artículos que indicaran o contraindicaran el uso del denosumab. Resultados: De un total inicial de 4306 artículos, se analizaron 18 artículos que mostraban consenso en la dosis y los controles con tomografía e indicaban o contraindicaban el uso del denosumab. Conclusiones: El denosumab está indicado como una buena opción de tratamiento preferente de tumores vertebrales primarios inoperables, para evitar recidivas o demorar las metástasis de tumores primarios o de tumores sólidos, principalmente de mama, próstata y pulmón, y para el compromiso vertebral del mieloma múltiple. El denosumab está contraindicado, por el momento, para las lesiones infecciosas. Nivel de Evidencia: III

Background: Denosumab is a human monoclonal antibody that acts against RANKL, inhibiting bone destruction mediated by osteoclasts, thus avoiding bone loss. For this reason, it is used in the treatment of osteoporosis as an antiresorptive and is authorized for the treatment of giant cell tumor and multiple myeloma. Our objective is to understand its indications and contraindications for the treatment of non-osteoporotic bone loss. materials and methods: A systematic review of English-language articles published between 2009 and 2023, using PRISMA criteria. Articles indicating or contraindicating the use of denosumab were considered for inclusion. Results: From a total of 4306 articles, 18 articles were analyzed, which showed consensus on the dose and controls with tomography and indicated or contraindicated the use of denosumab. Conclusions: Denosumab is recommended as a primary therapeutic option for unresectable spinal tumors, to prevent recurrences or to delay the formation of metastases from primary tumors or solid tumors, primarily breast, prostate, and lung, as well as for multiple myeloma spinal involvement. Denosumab is currently contraindicated in infectious lesions. Level of Evidence: III

Osteonecrose dos maxilares relacionada ao uso demedicamentos: características patológicas, diagnóstico,prevenção e estratégias terapêuticas / Medication-related osteonecrosis of the jaws: pathological characteristics, diagnosis, prevention and therapeutic strategies

Objetivo: Este trabalho tem como propósito fornecer uma análise abrangente das características clínicas, etiológicas, radiográficas e histopatológicas da osteonecrose dos maxilares relacionada ao uso de medicamentos, além de abordar os métodos de diagnóstico, prevenção e estratégias terapêuticas. Materiais e métodos: foi realizada uma busca por artigos científicos publicados no período de 2015 a 2023, utilizando as bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) e ScienceDirect. Conclusão: Embora infrequente, há um considerável potencial de ocorrência de osteonecrose dos maxilares em pacientes submetidos a terapia prolongada com medicamentos antirreabsortivos e antiangiogênicos, especialmente quando não são adotadas medidas preventivas adequadas. A implementação de práticas preventivas, a vigilância das condições bucais e a colaboração de uma equipe multidisciplinar são fundamentais para reduzir os riscos associados a essa condição patológica.(AU)

Objective: This work aims to provide a comprehensive analysis of the clinical, etiological, radiographic and histopathological characteristics of Medication-Related Jaw Osteonecrosis, in addition to addressing diagnostic methods, prevention and therapeutic strategies. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023, using the Scientific Electronic Library Online (SciELO), US National Library of Medicine (PubMed) and ScienceDirect databases. Conclusion: Although infrequent, there is a considerable potential for osteonecrosis of the jaw to occur in patients undergoing prolonged therapy with antiresorptive and antiangiogenic medications, especially when adequate preventive measures are not adopted. The implementation of preventive practices, surveillance of oral conditions and the collaboration of a multidisciplinary team are essential to reduce the risks associated with this pathological condition.(AU)

Analysis of Denosumab by a Validated CZE Method and Determination of Sialic Acids by the RP-HPLC Method.

A capillary zone electrophoresis (CZE) method was developed and validated to quantitate the monoclonal antibody denosumab (DmAb) and its charge variants in pharmaceutical products, demonstrating excellent precision, linearity and accuracy. Separations were obtained with migration times of 11.3 min for DmAb and the calibration curve was linear in the range of 0.95-20 mg/mL. The analytical comparability of seven batches of Prolia® showed mean differences of the estimated content/potencies of 1.87% lower, and 0.84 and 1.21% higher compared with the size-exclusion and reversed-phase liquid chromatography (SE-HPLC and RP-HPLC) methods and the osteoclast antiproliferative bioassay, respectively, with non-significant differences (P > 0.05). An RP-HPLC method with fluorescence detection (RP-HPLC-F), performed on a Kinetex® EVO C18 column (5 µm, 100 Å, 250 mm × 4.6 mm), was optimized to determine the levels of sialic acids of DmAb biomolecules, giving mean concentrations of 0.16 and 0.17 µg N-acetylneuraminic acid/mg DmAb for Prolia® and Xgeva® pharmaceutical products, respectively. The results demonstrated the capability of each one of the methods, and their use in combination constitutes a strategy to monitor instability, thereby assuring the quality and the batch-to-batch consistency of the biotechnology-derived medicine.

Osteonecrosis maxilar asociada con altas dosis de antirresortivos en paciente oncolólgico adulto mayor: resolución interdisciplinaria de caso clínico / Osteonecrosis of the jaw associated with high doses of antiresorptive in an elderly cancer patient: interdisciplinary resolution of a clinical case

La osteonecrosis maxilar relacionada con medicamentos (ONMM) es una patología de características clínicas objetivas con signo-sintomatología patogno-mónica. El criterio clínico aceptado es la presencia de hueso necrótico expuesto y visible sobre el reborde óseo maxilar que no ha cicatrizado luego de 8 sema-nas, en pacientes con antecedentes de tratamiento antirresortivo. La denominación relacionada con medicamentos se utiliza por el creciente número de casos asociados con otros fármacos antirresortivos como denosumab y con terapias antiangiogénicas, más allá de la conocida relación con bifosfonatos. Si bien la incidencia de ONMM en pacientes tratados por osteopatías metabólicas es muy baja, la situa-ción se torna más compleja en pacientes oncológicos con altas dosis de antirresortivos para tratamiento de metástasis ósea. Varios informes de casos des-criben cuadros de ONMM en pacientes con cáncer que reciben terapias dirigidas, específicamente TKI (inhibidores de tirosina kinasa) y anticuerpos mo-noclonales-VEGF (anticuerpos dirigidos al factor de crecimiento del endotelio vascular). La ONMM afecta negativamente la calidad de vida del paciente onco-lógico y produce comorbilidad significativa. Resulta imperioso identificar los pacientes en riesgo y dise-ñar un protocolo de atención odontológica específico para estos casos. En este artículo, se presenta un caso de ONMM asociado con altas dosis de Deno-sumab y administración simultánea de anticuerpos monoclonales específicos. El caso sorprende por la magnitud de la necrosis y su cuadro insidioso. El pro-tocolo de tratamiento descripto permitió controlar el cuadro inicial, limitar el avance de la lesión, asegurar el control del dolor y la infección, y finalmente, la cu-ración total de la lesión (AU)

Medication-related osteonecrosis of the jaws (MRONJ) is a pathology with objective clinical characteristics with pathognomonic signs and symp-toms. The accepted clinical criterion is the presence of exposed and visible necrotic bone on the maxillofacial region that has not healed after 8 weeks, in patients with history of antiresorptive treatment. The name medication-related is justified by the growing number of cases associated with other antiresorptive drugs such as denosumab and antiangiogenic therapies, beyond the known relationship with bisphosphonates. Although the incidence of MRONJ in patients treated for metabolic osteopathies is very low, the situation becomes more complex in cancer patients who re-ceive high doses of antiresorptives for the treatment of skeletal metastases. Several case reports describe the presence of MRONJ in cancer patients receiving targeted therapies, specifically TKI (tyrosine kinase inhibitors) and monoclonal antibodies-targeting VEGF (vascular endothelial growth factor). MRONJ nega-tively affects the quality of life in cancer patients and produces significant comorbidity. It is imperative to identify patients at risk and design a specific den-tal care strategy for these cases. In this article, we present a case of MRONJ associated with high doses of Denosumab and simultaneous administration of specific monoclonal antibodies. The case is surpris-ing due to magnitude of the necrosis. The described treatment strategies made it possible to control the initial symptoms, limit the lesion progression, ensure pain and infection control, and finally, the total heal-ing of the lesion (AU)

Long-term consequences of osteoporosis therapy with denosumab.

Denosumab (DMAb) is a human monoclonal antibody used as an antiresorptive drug in the treatment of osteoporosis. Approval at a dosage of 60 mg every 6 months was based on the results of the randomized, placebo-controlled trial (FREEDOM). The design of this 3-year study included an extension for up to 10 years. Those who were randomized to DMAb continued on drug, while those who were randomized to placebo transitioned to DMAb. The 10-year experience with DMAb provides data on efficacy of drug in terms of reduced fractures and continued increases in bone mineral density (BMD). The 10-year experience with denosumab also provides information about rare complications associated with the use of DMAb, such as osteonecrosis of the jaw (ONJ), and atypical femoral fractures (AFF). This experience provided new insights into the reversibility of effects upon discontinuation without follow-on therapy with another agent. This review focuses upon prolonged treatment with DMAb, with regard to beneficial effects on fracture reduction and safety. Additionally, its use in patients with impaired renal function, compare its results with those of bisphosphonates (BPs), the occurrence/frequency of complications, in addition to the use of different tools, from imaging techniques to histological findings, to evaluate its effects on bone tissue.

The why and how of sequential and combination therapy in osteoporosis. A review of the current evidence.

It is now well recognized that over the lifetime of a patient with osteoporosis, more than one medication will be needed to treat the disease and to decrease fracture risk. Though current gaps in osteoporosis therapy can be potentially mitigated with sequential and combination regimens, how to move seamlessly amongst the multiple treatments currently available for osteoporosis for sustained efficacy is still unclear. Data from recent studies show that an anabolic agent such as teriparatide or romosozumab followed by an antiresorptive affords maximal gain in BMD and possibly better and earlier fracture risk reduction compared to a regimen which follows the opposite sequence. Sequentially moving to a bisphosphonate such as alendronate from an anabolic agent such as abaloparatide has also been shown to preserve the fracture reduction benefits seen with the latter. This sequence of an anabolic agent followed by an antiresorptive should especially be considered in the high-risk patient with imminent fracture risk to rapidly reduce the risk of subsequent fractures. The data surrounding optimum timing of initiation of bisphosphonate therapy following denosumab discontinuation is still unclear. Though data suggests that combining a bisphosphonate with teriparatide does not provide substantial BMD gains compared to monotherapy, the concomitant administration of denosumab with teriparatide has been shown to significantly increase areal BMD as well as to increase volumetric BMD and estimated bone strength. This narrative review explores the available evidence regarding the various sequential and combination therapy approaches and the potential role they could play in better managing osteoporosis.

Erythema nodosum with incidental calciphylaxis secondary to zoledronic acid and denosumab.

Erythema nodosum (EN) is the most common clinical presentation of panniculitis, an inflammatory process that affects subcutaneous cellular tissue, characterized by the acute appearance of painful erythematous nodules predominantly in the lower extremities. An unusual case of EN is presented below, secondary to the administration of zoledronic acid (ZA) and denosumab, in which incidental histopathological findings of calciphylaxis were also found.

Denosumabe e osteonecrose dos maxilares: o que o cirugião-dentista precisa saber? / Denosumab and osteonecrosis of the jaws: what does the dental surgeon need to know? / Denosumab y osteonecrosis de mandíbulas: ¿qué necesita saber el cirujano dental?

Introdução:O Denosumabeé um fármaco antirreabsortivo indicado para o tratamento de osteoporose e doenças ósseas metastáticas. O seu uso está associado ao desenvolvimento de reações adversas em diferentes órgãos, como a osteonecrose dos maxilares, que é o evento adverso de interesseodontológico. Objetivo:Realizar um levantamento bibliográfico sobre o mecanismo de ação do Denosumabe no tecido ósseo e destacar a importância do cirurgião-dentista na prevenção, no diagnóstico e tratamento da osteonecrose nos maxilares.Metodologia:Trata-se de uma revisão integrativa elaboradaem duas etapas: inicialmente realizou-se uma busca de artigos publicados entre os anos 2010a 2022, sobre a osteonecrose em pacientes que fazem uso do Denosumabe nas plataformas de dados Pubmed, ScieloeBiblioteca Virtual em Saúde. Posteriormente, foi feita uma seleção de partes relevantes para a pesquisa, uma leitura analítica e a organização das informações coletadas pertinentes a cada tópico da pesquisa.Resultados:ODenosumabe inibea ligação da citocina RANKL ao seu receptor RANK, tal mecanismo de ação reduz o processo de reabsorção óssea execessiva. As osteonecroses podem apresentar-se em diferentes níveis de estadiamento e caracterizam-se como área de exposição óssea necrótica na região maxilofacial, permanecendo por mais de oito semanas e sem histórico de radioterapia ou doença metastática evidentes nos maxilares. Alguns fatores predispõem o desenvolvimento das osteonecroses, entre eles: procedimentos odontológicos cirúrgicos. Ainda não existe um protocolo de tratamento definitivo, entretanto, modalidades terapêuticas coadjuvantes são administradas de acordo com a condição clínicado paciente.Conclusões:O exame clínico deve ser minucioso, atentando-se a qualquer alteração na cavidade bucal, às doenças preexistentes e às medicações utilizadas pelo paciente. Em todos os casos deve-se, realizar orientações de higiene oral e adequação do meio bucal previamente ao tratamento oncológico e ao uso de drogas antirreabsortivas (AU).

Introduction:Denosumab is an antiresorptive drug indicated for the treatment of osteoporosis and metastatic bone diseases. Its use is associated with the development of adverse reactions in different organs, such as osteonecrosis of the jaws, which is an adverse event ofdentalinterest.Objective:Conducta bibliographic survey on the mechanism of action of Denosumab in bone tissue and to highlight the importance of the dentist in the prevention, diagnosis and treatment of osteonecrosis in the jaws. Methodology: This is an integrative review carried out in two stages: initially, a search was carried out for articles published between the years 2010to 2022, on osteonecrosis in patients using Denosumab in the data platforms Pubmed, Scieloand Virtual Health Library(BVS). Subsequently, a selection of relevant parts for the research was made, an analytical reading and the organization of the collected information pertinent to each research theme was carried out.Results:TheDenosumab inhibitsthe binding of the RANKL cytokine to its RANK receptor, this mechanism of action reduces the process of excessive bone resorption. Osteonecrosis can present at different staging levels and are characterized as an area of necrotic bone exposure in the maxillofacial region, lasting for more than eight weeks and without a history of radiotherapy or evident metastatic disease in the jaws. Some factors predispose the development of osteonecrosis, including: surgical dental procedures. There is still no definitive treatment protocol, however, supporting therapeutic modalities are administered according to the patient's clinical condition.Conclusions:The clinical examination must be thorough, paying attention to any changes in the oral cavity, pre existing diseases and medications used by the patient. In all cases, guidelines on oral hygiene and adequacy of the oral environment should be carried out prior to oncological treatment and the use of antiresorptive drugs (AU).

Introducción: Denosumab es un fármaco antirresortivo indicado para el tratamiento de la osteoporosis y enfermedades óseas metastásicas. Su usoestá asociado al desarrollo de reacciones adversas en diferentes órganos, comola osteonecrosis de los maxilares, que es un evento adverso de interés odontológico. Objetivo: Realizar un levantamiento bibliográfico sobre el mecanismo de acción de Denosumab en el tejido óseo y resaltar la importancia del odontólogo en la prevención, diagnóstico y tratamiento de la osteonecrosis en los maxilares. Metodología: Esta es una revisión integradora realizada en dos etapas: inicialmente se realizó una búsqueda de artículos publicados entre los años 2010 a 2022, sobre osteonecrosis en pacientes usuarios de Denosumab en las plataformas Pubmed, ScieloyBiblioteca Virtual en Salud(BVS).Posteriormente, se realizó una selección de partes relevantes para la investigación, se realizó una lectura analítica y la organización de la información recolectada relevante para cada tema de investigación. Resultados:Denosumab inhibela unión de la citoquina RANKL a su receptor RANK, este mecanismo de acción reduce el proceso de reabsorción ósea excesiva. La osteonecrosis puede presentarse en diferentes nivelesde estadificación y se caracterizan por un área de exposición ósea necrótica en la región maxilofacial, con una duración mayor a ocho semanas y sin antecedentes de radioterapia o enfermedad metastásica evidente en los maxilares. Algunos factores predisponen al desarrollo de osteonecrosis, entre ellos: procedimientos quirúrgicos dentales. Aún noexiste un protocolo de tratamiento definitivo, sin embargo, se administran modalidades terapéuticas de apoyo de acuerdo a la condición clínica del paciente.Conclusiones: El examen clínico debe ser minucioso, prestando atención a cualquier cambio en la cavidad bucal, enfermedades preexistentes y medicamentos utilizados por el paciente. En todos los casos se deben realizar pautas de higiene bucal y adecuación del medio bucal previo al tratamiento oncológico y al uso de fármacos antirresortivos (AU).

[Experience with Denosumab in central giant-cell granuloma]. / Experiencia con Denosumab en granuloma central de células gigantes.

INTRODUCTION: Central Giant Cell Granuloma is an infrequent bone lesion located mainly in the maxillary bone. The main treatment is surgery with wide margins, so it sometimes causes great morbidity and esthetic al terations. Denosumab, a RANK-ligand inhibitor monoclonal antibody, has been presented as a valid therapeutic alternative in the treatment of these lesions. OBJECTIVE: to describe the clinical and radio logical response after treatment with Denosumab in a patient with unresected giant cell granuloma. CLINICAL CASE: 12-year-old boy who consulted due to a 24-hour maxillary swelling, without other associated symptoms. Examination revealed a tumor in the upper left maxilla with bulging of the ip- silateral gingiva. A CT scan was performed which showed a large expansive intraosseous lesion in the maxillary alveolar ridge. The biopsy of the lesion was compatible with Central Giant Cell Granuloma. Due to the size and location of the lesion, initial treatment with Denosumab, a human monoclonal antibody with action on RANK-ligand, was indicated. After 10 months of treatment, the patient showed a favorable clinical and radiological response, with a size decrease of the lesion and metabolic activity. As an adverse effect, the boy presented mild hypocalcemia, resolved after supplementation with calcium. CONCLUSION: the use of Denosumab as the first line of treatment in Giant Cell Granu loma may be an adequate therapeutic option in adolescents with lesions that are difficult to resect.

Denosumabe e teriparatida para o tratamento indivíduos com osteoporose grave e falha terapêutica aos medicamentos disponíveis no Sistema Único de Saúde / Denosumab and teriparatide for the treatment of individuals with severe osteoporosis and therapeutic failure to the drugs available in the Unified Health System

INTRODUÇÃO: A osteoporose, doença que aumenta da fragilidade óssea e suscetibilidade à fratura, afeta cerca de 200 milhões de pessoas no mundo. No geral, a prevalência de osteoporose em estudos brasileiros varia de 6% a 33% dependendo da população e outras variáveis avaliadas. Entre os indivíduos com osteoporose, aqueles que apresentaram fratura osteoporótica têm duas vezes o risco para nova fratura. Para evitar novas fraturas, o tratamento preconizado deve incluir estratégias medicamentosas e não medicamentosas. Entre as medicamentosas, suplementação de cálcio e colecalciferol, alendronato, risedronato, pamidronato, raloxifeno, calcitonina e estrógenos conjugados são opções disponíveis no Protocolo Clínico de Diretrizes Terapêuticas (PCDT) de Osteoporose do Sistema Único de Saúde (SUS). Apesar da disponibilidade de tratamentos, estima-se que 25% dos pacientes continuam a apresentar falha terapêutica aos tratamentos disponíveis. Nesse contexto, as diretrizes clínicas nacionais e internacionais de sociedade médicas, recomendam o uso de denosumabe ou teriparatida a pacientes com osteoporose grave e falha terapêutica aos medicamentos disponíveis no SUS (alendronato, pamidronato, raloxifeno e risedronato). Entretanto, há incerteza se os benefícios identificados para população em tratamento de primeira linha, principal população incluída nos estudos, são sustentados em população com osteoporose grave e falha terapêutica em vigência de tratamento; e se a escolha, por estas opções terapêuticas, pode valer a pena e ser viável economicamente para o SUS. Assim, o objetivo do presente relatório é analisar as evidências científicas sobre eficácia, efetividade, segurança, bem como evidências econômicas do denosumabe e da teriparatida para o tratamento de pacientes com osteoporose grave com falha terapêutica aos medicamentos disponíveis no SUS (alendronato, pamidronato, raloxifeno e risedronato). TECNOLOGIAS: Denosumabe (Prolia®) e teriparatida (Fortéo®). PERGUNTA: Os medicamentos denosumabe e

Denosumabe para o tratamento de osteoporose e doença renal crônica em estágio 4 e 5 / Denosumab for the treatment of osteoporosis and chronic kidney disease 4 and 5

INTRODUÇÃO: A osteoporose é uma doença osteometabólica sistêmica comum, caracterizada pela diminuição da massa óssea e deterioração da microarquitetura do tecido ósseo, resultando em fragilidade óssea, o que predispõem ao aumento do risco de fratura. Além de fraturas osteoporóticas, os pacientes podem ser acometidos de maiores complicações clínicas como dor crônica, depressão, deformidade, perda da independência e aumento da mortalidade. Os distúrbios minerais e ósseos também são importantes complicações da DRC, visto que há a deterioração progressiva da homeostase mineral, resultando em várias consequências clínicas, como fraturas, dores ósseas, deformidades esqueléticas, calcificação vascular, doença cardiovascular e morte. A prevenção destes distúrbios no metabolismo mineral e ósseo e seu manejo no início do curso da DRC são muito importantes na melhora da qualidade de vida destes pacientes. Na população em geral, a prevenção de fraturas com bifosfonatos está bem estabelecida, no entanto, bifosfonatos orais contendo nitrogênio são excretados pelos rins, limitando as opções de tratamento para osteoporose em pessoas com DRC. Neste contexto, o denosumabe pode ser uma alternativa ao tratamento de pacientes com osteoporose e DRC em estágios avançados (TFG< 30mL/min). TECNOLOGIAS: Denosumabe. PERGUNTA: O denosumabe é eficaz, efetivo, seguro e custo efetivo quando comparado ao uso de pamidronato, calcitonina, estrógenos conjugados ou placebo2 para o tratamento de pacientes com osteoporose e DRC em estágios 4 e 5 (TFG < 30mL/min)? EVIDÊNCIAS CLÍNICAS: Foram encontrad

Comparação entre métodos cirúrgicos e conservadores para o tratamento de granuloma central de células gigantes descritos na literatura / Comparison between surgical and conservative methods for the treatment of central granuloma of giant cells described in the literature

Objetivo: Apresentar, através de uma revisão de literatura, métodos de tratamento do Granuloma mais conservadores, estabelecendo comparações entre estes, afim de fornecer à comunidade científica mais clareza e opções mais efi-cazes e seguras para o paciente. Revisão da literatura:O Granuloma Central de Células Gigantes (GCCG) é uma lesão proliferativa benigna intraóssea de etiologia incerta e comportamento clínico variável que possui como forma de tratamento mais utilizado os métodos cirúrgicos, entretanto, observou-se que os métodos cirúrgicos apresentam alta taxa de recidiva e um grande comprometimento estético e funcional. Em contrapartida, métodos mais conserva-dores mostram regressão completa da lesão e baixa taxa de recidiva, porém com a desvantagem de apresentar um longo período de tratamento e alguns efeitos adversos. Discussão: Ainda não existe um protocolo de gerenciamento de GCCG, seu manejo clínico deve levar em consideração a possibilidade de combinação de duas ou mais terapias objetivando melhores resultados. Conclusão: Os métodos conservadores são promissores por diminuir o tempo de tratamento e preservar a estética e função, além de ter a possibilidade de serem empregados juntos conforme a necessidade do paciente, apesar de nenhuma forma de tratamento individual ser a ideal.

Aim: To present, through a literature review, more conservative methods of treatment for Granuloma, establishing comparisons between them, in order to provide the scientific community with more clarity and more effective and safer options for the patient. Literature review: The Central Giant Cell Granuloma (GCCG) is a benign proliferative intraosseous lesion of uncertain etiology and variable clinical behavior that has surgical methods as the most used form of treatment, however, it was observed that surgical methods have a high recurrence rate and a great aesthetic and functional compromise. On the other hand, more conservative methods show complete regression of the lesion and a low recurrence rate, but with the disadvantage of presenting a long period of treatment and some adverse effects. Discussion: There is no protocol for managing GCCG, its clinical management should consider the possibility of com-bining two or more therapies aiming at better results. Conclusion: Conservative methods are promising for reducing treatment time and preserving aesthetics and function, in addition to having the possibility of being used together according to the patient's need, although no individual treatment is ideal.

Osteonecrosis mandibular: hallazgos clínicos e imagenológicos en un paciente tratado con denosumab / Mandibular osteonecrosis: clinical and imaging findings in a patient treated with denosumab

Introducción: La administración de bifosfonatos y medicamentos antiangiogénicos en pacientes con cáncer es un esquema terapéutico usual en oncología. Existen reportes de osteonecrosis de los maxilares en pacientes sometidos a este esquema de tratamiento, luego de realizar un procedimiento dental invasivo. Objetivo: A partir de las características clínicas e imagenológicas de la patología, ilustrar al odontólogo sobre los medicamentos para el tratamiento del cáncer, susceptibles de generar osteonecrosis de los maxilares. Presentación de caso: Paciente masculino de 89 años, con cáncer de próstata tratado con denosumab, que desarrolló osteonecrosis del maxilar inferior posterior a una extracción dental. Es de vital importancia que el odontólogo identifique los medicamentos, factores de riesgo y las medidas para minimizar el riesgo de osteonecrosis de los maxilares en pacientes susceptibles(AU)

Introduction: The administration of bisphosphonates and antiangiogenic drugs in cancer patients is a usual therapeutic scheme in oncology. There are reports of osteonecrosis of the jaws in patients undergoing this treatment scheme, after performing an invasive dental procedure. Objective: Show the dentist from the clinical and imaging characteristics of the pathology on the drugs for the treatment of cancer sensitivity to generate osteonecrosis of the jaws. Case presentation: An 89-year-old male patient with prostate cancer treated with denosumab developed osteonecrosis of the lower jaw after tooth extraction. It is vitally important that the dentist identifies medications, risk factors and measures to minimize the risk of osteonecrosis of the jaws in sensitivy patients(AU)

Uso de denosumab en quiste óseo aneurismático: revisión de la literatura / Use of denosumab in aneurysmatic bone cyst: literature review

INTRODUCCIÓN Los quistes óseos aneurismáticos (QOAs) son tumores benignos, localmente agresivos, y con importante potencial de recidiva, que representan aproximadamente el 1% de todos los tumores óseos. Se describen múltiples tratamientos, como: escisión intralesional, embolización arterial selectiva, inyección de agentes esclerosantes, y radiación. Estos tratamientos tienen una tasa variable de eficacia, ya que la recurrencia puede llegar al 20% y puede estar asociada a comorbidades graves como la pérda funcional de la extremidad. OBJETIVO Realizar una revisión integradora de la literatura sobre el uso de denosumab para el tratamiento de QOAs, describiendo el perfil epidemiológico, la dosis utilizada, y las complicaciones. MÉTODO Se recopilaron artículos publicados en los últimos cinco años en la base de datos PubMed. La información recogida de los casos reportados fue la edad, el sexo, la ubicación del tumor, la realización de cirugía antes y/o después del tratamiento con denosumab, la dosis utilizada, las complicaciones, y la recurrencia. RESULTADOS Se analizaron 7 artículos, 4 reportes de casos y 3 series de casos, escritos en inglés, y publicados de 2014 a 2019. La mayoría de los pacientes eran del sexo femenino, con una edad promedio de 14 años, y el tumor localizado en la columna. CONCLUSIÓN El uso de denosumab en el tratamiento de QOAs ha tenido una buena respuesta, ya que tiene bajas tasas de recurrencia y complicaciones; sin embargo, hacen falta más estudios para definir el protocolo de tratamiento.

INTRODUCTION Aneurysmal Bone Cysts (ABCs) are locally-aggressive benign tumors with relevant potential for recurrence, representing approximately 1% of all bone tumors. Multiple treatments are described for them, such as: intralesional excision, selective arterial embolization, injection of sclerosing agents, and radiation. These treatments have a variable efficacy rate, can reach 20% and may be associated with serious comorbidities such as functional loss of the limb. OBJETIVE To perform an integrative review of the literature on the use of denosumab in the treatment of ABCs, describing the epidemiological profile, the dosage used, and the complications. METHODOLOGY Articles published in the past five years were retrieved from the PubMed database. The information collected from the cases reported was age, gender, tumor location, the performance of surgery before and/or after the denosumab treatment, the dose used, the complications, and recurrence. RESULTS We analyzed 7 articles, 4 case reports and 3 case series, written in English, and published from 2014 to 2019. Most patients were female, with an average age of 14 years, with the tumor located in the spine. CONCLUSION The use of denosumab in the treatment of ABCs yielded good results, with low rates of recurrence and complications. However, further studies are needed to define a treatment protocol.

Osteonecrose dos maxilares associada a medicamentos em pacientes reabilitados com implantes / Drug-associated osteonecrosis of the jaw in patients rehabilitated with implants

A osteonecrose associada a medicamentos (OAM) é um dos principais efeitos colaterais a ser considerado no uso de medicações antirreabstorivas pois, em muitos casos, pode agravar significativamente a qualidade de vida do paciente, necessitando da realização de tratamentos radicais ou mesmo não existindo soluções para manejo desta condição. Na prática clínica temos observado um grande número de necroses desenvolvendo ao redor de implantes osteoitegrados (IOI), até mesmo, em implantes realizados antes do início da terapia antirreabsortiva. Foram estimados 149 pacientes divididos em dois grupos: Grupo A (osteonecrose sem envolvimento de IOIs) e Grupo B (osteonecrose associada a IOIs) avaliando clínica e radiograficamente, durante um período de 16 anos, a Osteonecrose associada a medicamentos (OAM) em pacientes reabilitados com IOI, além de estabelecer uma relação entre o tempo e número de aplicações dos medicamentos com o tempo de colocação dos IOI e o desenvolvimento da OAM. Foram analisados exames de imagem, além de serem coletadas informações clínicas dos prontuários eletrônicos, de pacientes que fizeram e/ou fazem uso de Bisfosfonatos ou Denosumabe tanto para o tratamento de osteoporose como para o tratamento de metástases ósseas, os quais foram reabilitados com IOI e apresentaram OAM. O tempo de uso da medicação foi superior em pacientes do Grupo B sendo 3,3 anos com variação de 3 a 9 anos. Dentre os pacientes do Grupo B, o Zometa foi a medicação mais utilizada (40%), com diferença estatística encontrada (p < 0,02). Observou-se que um total de 121 pacientes (82,3%) não receberam avaliação odontológica prévia ao início da medicação e que para 117 pacientes (79,6%) a cirurgia de debridamento ósseo foi o tratamento de escolha. Em relação a quantidade de aplicações, foi observado uma média de 34 aplicações para os pacientes do Grupo B. Os resultados corroboram com a literatura, onde o medicamento, a quantidade de aplicações e o momento em que foi realizada a cirurgia de colocação dos IOIs influenciam no prognóstico do caso

Drug-associated osteonecrosis (OAM) is one of the main drug-related effects considered to be anti-resorptive because, in many cases, it can significantly worsen the patient's life, requiring quality of radical treatments or even lacking solutions for the management of this condition. In clinical practice, we have many antiresorptive necrosis implants around osteogenic implants (IOI), even performed before the start of therapy. We estimated 149 patients during the two groups: Group A osteonecrosis without involvement of IOIs) and Group B (osteonecrosis associated with IOIs) evaluating clinically and radiographically, a period of 16 years, a prevalence of osteonecrosis associated with medication (MOA) in rehabilitated patients. with IOI, in addition to establishing a relationship between the time and number of drug applications with the time of placement of the IOI and the development of OAM. Imaging exams will be examined, in addition to collecting clinical information from electronic medical records, who made and/or use Bisphosphonates or Denosumab both for the treatment of osteoporosis and the treatment of bone metastases, which were reassessed with IOI and presented OAM. The duration of medication use was higher in patients in Group B 3.3 years with a duration of 3 to 9 years. Among the patients in Group B, Zometa was the most used medication (40%), a statistical difference was found (p < 0.02). Note that a total of 21 patients (82.3%) did not receive dental surgery prior to the beginning of the choice of 19 patients and that 117 patients (7.6%) underwent bone treatment. Regarding the number of applications, observed from an average of patients in Group B. The results corroborate, where the drug, which was performed in a surgery of number of applications in IOI placement, was used for a surgery of nonprognostic number of applications of the case

Osteonecrosis de los maxilares asociada a drogas antirresortivas en pacientes osteoporóticos: presentación de un caso clínico / Antiresorptive drugs-related jaw osteonecrosis in osteoporotic patients: report of a clinical case

La osteoporosis se caracteriza por una masa ósea baja con deterioro de la microarquitectura del tejido que conduce a la fragilidad, lo que aumenta el riesgo de fracturas. Después de la menopausia, la deficiencia de estrógenos aumenta la exposición del tejido al ligan- do RANK, lo que resulta en un aumento de la reabsorción y pérdida ósea, que pueden provocar osteoporosis. (1) Los bifosfonatos y el denosumab son utilizados para el tratamiento de la osteoporosis debido a su capacidad anticatabólica, que reducen la remodelación previniendo la pérdida de masa ósea, disminuyendo la probabilidad de fracturas y aumentando la densidad mineral del tejido. (2) La osteonecrosis de los maxilares asociadas a drogas antirresortivas es una situación que se presenta en pacientes que consumen de manera crónica antirresortivos para el tratamiento de enfermedades como: osteoporosis, osteogénesis imperfecta, enfermedad de Paget, displasia fi- brosa, hipercalcemia maligna asociada a tratamiento oncológico (AU)

Osteoporosis is characterized by low bone mass with deterioration of the tissue microarchitec- ture leading to fragility, which increases the risk of fractures. After menopause, estrogen deficiency increases tissue exposure to the RANK ligand, resulting in increased bone loss and resorption, which can lead to osteoporosis. (1) Bisphosphonates and denosumab are used for the treatment in low concentration, due to their anticatabolic capacity, which reduce remodeling, preventing loss of bone mass and fractures besides, antiresorptives drugs increase the mineral density of the tissue. (2) Osteonecrosis of the jaw associated with antiresorptives drugs occurs in patients whose chro- nically consume these drugs for the treatment of diseases such as: osteoporosis, imperfect osteogenesis, Paget's disease, fibrous dysplasia, malignant hypercalcemia associated with oncological treatment (AU)