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)

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)

Effects of denosumab on bone mineral density around proximal femoral prosthesis after total hip replacement in postmenopausal osteoporotic patients / 中国骨伤

OBJECTIVE@#To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients.@*METHODS@#Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured.@*RESULTS@#At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation.@*CONCLUSION@#After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.

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).

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.

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)

Which is the best antiresorptive treatment after finishing teriparatide? / ¿Cuál es el mejor tratamiento antirresortivo luego de terminar con teriparatide?

Abstract Anabolic drugs are the treatment of choice for osteoporotic patients with very high risk of fractures. Post anabolic treatment with an antiresorptive drug maintains the bone mineral density (BMD) gained. The recommendations regarding the ideal antiresorptive drug are not precise. The aim of this paper is to compare the usefulness of zoledronate and denosumab in a group of 28 women with very high risk of fractures. All of them completed at least one year of treatment with teripatide and latter 14 received zolendronate and 14 denosumab for another year. We retrospectively review their biochemical and densitometric changes. Both treat ment groups experienced a reduction in bone turnover markers of the same magnitude at the end of the second year. In Lumbar Spine BMD increase of 3.96 ± 8.56% Median (Me) 2.54 p = 0.21 in zolendronate group and 3.55 ± 5.36% (Me 5.14) p = 0.07 in denosumab group. Femoral Neck BMD changed -0.09 ± 6.50% (Me 0.29) p = 0.85 in zolendronate group, and - 3.41 ± 5.08% (Me 5.35) p = 0.59 in denosumab group, with no difference between both groups. In Total Hip BMD an increase of 0.55 ± 4.20% (Me 0.43) p = 0.70 in zoledronate group, and 4.53 ± 5.13% (Me 0.64) p = 0.04 with denosumab. We conclude that both antiresortive treatments have a similar effect in biochemical markers after one year of treatment. BMD increase significantly in total hip and changed with a trend toward in lumbar spine with denosumab, but without differences between both groups of treatment.

Resumen Los anabólicos son el tratamiento de elección en la osteoporosis con muy alto riesgo de fracturas. Después del tratamiento anabólico un fármaco antirresortivo mantiene la densidad mineral ósea (DMO) ganada. Las reco mendaciones sobre el fármaco antirresortivo ideal no son precisas. El objetivo de este trabajo es comparar la utilidad de zoledronato y denosumab en un grupo de 28 mujeres con muy alto riesgo de fracturas. Todas ellas completaron al menos un año de tratamiento con teripatide y luego 14 recibieron zolendronato y 14 denosumab durante un año. Revisamos retrospectivamente sus cambios bioquímicos y densitométricos. Ambos grupos de tratamiento experimentaron una reducción de los marcadores de recambio óseo de la misma magnitud al final del segundo año. En columna lumbar la DMO aumentó 3.96 ± 8.56% Mediana (Me) 2.54, p = 0.21 en el grupo zolendronato y 3.55 ± 5.36% (Me 5.14) p = 0.07 en el grupo denosumab. La DMO del cuello femoral cambió -0.09 ± 6.50% (Me 0.29) p = 0.85 en el grupo zolendronato y - 3.41 ± 5.08% (Me 5.35) p = 0.59 en el grupo de denosumab, sin diferencias entre ambos grupos. En la Cadera Total la DMO aumentó 0.55 ± 4.20% (Me 0.43) p = 0.70 con zoledronato y 4.53 ± 5.13% (Me 0.64) p = 0.04 con denosumab. Concluimos que ambos tratamien tos antiresortivos tuvieron un efecto similar en los marcadores bioquímicos después de un año de tratamiento. La DMO aumentó significativamente en la cadera total y mostró una tendencia similar en columna lumbar con denosumab, sin diferencias entre ambos tratamientos.

Denosumab como tratamiento neoadyuvante del tumor de células gigantes del hueso. Indicaciones, resultados y efectos adversos / Denosumab as a neoadjuvant treatment for giant cell tumor of bone. Indications, results and side effects

Resumen El tumor de células gigantes óseo es una neoplasia de agresividad local intermedia, que raramente metastatiza. En los últimos años el denosumab, anticuerpo monoclonal humano, surgió como una alternativa de tratamiento para esta enfermedad, al bloquear el comportamiento lítico tumoral. El objetivo de este trabajo fue determinar sus indicaciones y efectos adversos, analizando también los resultados oncológicos, y las tasas de recurrencia local en pacientes con diagnóstico de tumor de células gigantes óseo que recibieron denosumab como tratamiento neoadyuvante. Entre 2010 y 2018 se analizaron 80 pacientes con tumor de células gigantes, de los cuales 14 recibieron denosumab como tratamiento neoadyuvante. El seguimiento mínimo fue 12 meses. En 8 pacientes se trató de un tumor primario, mientras que 6 fueron pacientes con recidiva tumoral. En todos los casos se evidenció una mejoría clínica. Trece presentaron cambios radiográficos, y 11 respuesta histológica completa. En 6 de 14 pacientes se evidenció una recurrencia local y en 7 se identificó al menos un efecto adverso relacionado con el denosumab (incluyendo una malignización tumoral). A pesar de ser una herramienta útil para el tratamiento del tumor de células gigantes, el uso de denosumab está asociado a mayor tasa de recurrencias locales y no está exento de efectos adversos.

Abstract Giant cell tumor of bone is an intermediate, locally aggressive and rarely metastasiz ing, primary bone neoplasia. In recent years denosumab emerged as a treatment alternative for this pathology. The objective of this work was to analyze its indications as well as the clinical outcomes, side effects and local recurrence rates in patients diagnosed with giant cell tumor of bone, who received denosumab as neoadjuvant treatment. Between 2010 and 2018, 80 patients with giant cell tumor were analyzed, of whom 14 received deno sumab as a neoadjuvant treatment. The minimum follow-up was 12 months. In 8 patients it was a primary tumor, while 6 showed tumor recurrence. In all cases, clinical improvement was evident. Thirteen patients presented radiographic changes, and 11 showed complete histological response. A local recurrence was evidenced in 6 of 14 patients, and at least one adverse effect related to denosumab (including tumor malignancy) was identified in 7. Despite being a useful tool for treating giant cell tumor, the use of denosumab is associated with a higher rate of local recurrences and is not free of adverse effects.

Uso de denosumab para el quiste óseo aneurismático de columna. Reporte de un caso y revisión bibliográfica / Use of denosumab in an aneurysmal bone cyst of the spine. Case report and literature review

Los tumores vertebrales de columna tienen una frecuencia muy baja. La incidencia de quiste óseo aneurismático es del 1-4% de todos los tumores. Su ubicación predominante es la columna lumbar, en mayor medida, en el arco posterior. Según estudios publicados, esta enfermedad se comporta de forma agresiva, por la compresión radicular que genera debido a su expansión. Si bien hay bibliografía sobre el tratamiento quirúrgico del tumor y su resección en bloque y embolización, no hay experiencias sobre el tratamiento con anticuerpos monoclonales. Existen muy pocos artículos que corroboren un tratamiento para las recidivas o los quistes óseos aneurismáticos inoperables o intralesionales, los cuales dejan la posibilidad abierta a otras técnicas. Presentamos el caso de una mujer de 38 años con lumbocruralgia. En los estudios, se detecta una tumoración, y la biopsia por punción y las imágenes confirman que se trata de un quiste óseo aneurismático. Se planifica el tratamiento con embolización preoperatoria y exéresis intracompartimental mediante cirugía posterior con liberación del saco dural. A los seis meses, el tumor recidiva. Se indica tratamiento con denosumab por dos años, se realizan controles periódicos y se constata la remisión de los síntomas y la mejoría de las imágenes. Nivel de Evidencia: IV

Vertebral tumors of the spine have a very low frequency. The incidence of aneurysmal bone cyst (ABC) ranges between 1% and 4% of all tumors. Its predominant location is the lumbar spine, to a greater extent, in the posterior arch. According to published studies, this condition behaves aggressively, due to the root compression generated by its expansion. While there is literature on the surgical treatment of the tumor and its en bloc resection and embolization, there is no experience on the treatment with monoclonal antibodies. There are very few published articles that corroborate a treatment for recurrences or for inoperable or intralesional aneurysmal bone cysts, which leave the possibility open to other techniques. We present the case of a 38-year-old woman with lumbar pain radiating to the thigh. In studies, a tumor was detected, and the needle biopsy and imaging confirmed that it was an aneurysmal bone cyst. We planned the treatment with preoperative embolization and intracompartmental excision by subsequent surgery with the release of the dural sac. At six months, tumor recurrence was observed. Treatment with denosumab was indicated for two years, periodic controls were carried out and the remission of symptoms and improvement in the images were verified. Level of Evidence: IV

Denosumab can be used successfully as a bridge to surgery in patients with severe hypercalcemia due to primary hyperparathyroidism

SUMMARY Severe hypercalcemia is a medical emergency that requires immediate and aggressive management. Primary hyperparathyroidism (PHPT) often causes severe hypercalcemia. Volume resuscitation, parenteral salmon calcitonin, and administration of intravenous bisphosphonates are common measures used to stabilize patients. However, the use of these measures is inadequate in several patients and may even be contraindicated in individuals with renal insufficiency or severe systemic illness. This study demonstrated the efficacy and safety of denosumab in patients with severe hypercalcemia due to PHPT, when immediate surgery was not feasible. We present four patients with severe hypercalcemia due to PHPT. Immediate surgery was not feasible because the patients had severe systemic illness, such as seizures and altered sensorium (case 1); acute severe pancreatitis (cases 2 and 3); or coronavirus disease 2019 pneumonia (case 4). Intravenous normal saline and parenteral salmon calcitonin were inadequate for controlling hypercalcemia. Intravenous bisphosphonates were avoided because of severe systemic illness in all cases and impaired renal function in three cases. Denosumab was administered to control hypercalcemia and allow the stabilization of patients for definitive surgical management. Following denosumab administration, serum calcium levels normalized, and general condition improved in all patients. Three patients underwent parathyroidectomy after two weeks and another patient after eight weeks. The use of denosumab for the management of severe hypercalcemia due to PHPT is efficacious and safe in patients when immediate surgical management is not feasible due to severe systemic illness.

Eficácia e segurança da Teriparatida comparada aos bifosfonados orais e Raloxifeno para prevenção de fraturas em osteoporose: revisão rápida de evidências / Effectiveness, safety and cost-effectiveness of Teriparatide compared to oral biposphonates or Raloxifene for osteoporotic fracture prevention: rapid review of evidence

Tecnologia: Teriparatida, comparada a bifosfonados orais ou Raloxifeno. Indicação: prevenção de fraturas em pessoas com osteoporose. Pergunta: A Teriparatida é mais eficaz e segura que os bifosfonados orais ou o Raloxifeno para tratamento da osteoporose e prevenção de fraturas secundárias à osteoporose? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews version 2 (AMSTAR-2). Resultados: Foram selecionadas 2 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: Para a população em geral com osteoporose, a Teriparatida evita mais fraturas vertebrais que o Alendronato de sódio ou Risedronato de sódio, mas efeito similar para fraturas não vertebrais. Teriparatida previne mais fraturas vertebrais e não vertebrais que Raloxifeno. Teriparatida tem maior efeito sobre a massa óssea corporal que o Risedronato de sódio e o Raloxifeno, mas tem efeito similar ao Alendronato de sódio. Na população masculina com osteoporose, a terapia com bifosfonados orais é mais eficaz que suplementação nutricional ou placebo para prevenir fraturas. Já o tratamento com Teriparatida não é mais eficaz que a suplementação nutricional ou placebo

Teriparatide compared to oral bisphosphonates or Raloxifene. Indication: prevention of fractures in people with osteoporosis. Question: Is Teriparatide more effective and safer than oral bisphosphonates or Raloxifene for treating osteoporosis and preventing fractures secondary to osteoporosis? Methods: Bibliographic survey was carried out in the PUBMED database, following predefined search strategies. Evaluation of the methodological quality of systematic reviews was carried out using the tool Assessing the Methodological Quality of Systematic Reviews version 2 (AMSTAR-2). Results: Two systematic reviews were selected, which met the inclusion criteria. Conclusion: For the general population with osteoporosis, Teriparatide prevents more vertebral fractures than Alendronate or Risedronate sodium, but has similar effect for non-vertebral fractures. Teriparatide prevents more vertebral and non-vertebral fractures than Raloxifene. Teriparatide has a greater effect on body bone mass than Risedronate sodium and Raloxifene, but it has a similar effect to Alendronate sodium. In the male population with osteoporosis, oral bisphosphonates is more effective than nutritional supplementation or placebo to prevent fractures. Treatment with teriparatide is no more effective than nutritional supplementation or placebo

Fundamentos de elección terapéutica: osteonecrosis maxilar asociada a drogas antirresortivas (MRONJ) / Fundamentals of therapeutic choice: anti-resorptive drug-related maxillary osteonecrosis (MRONJ)

La acción terapéutica favorable que los antirresortivos (bifosfonatos BPs, denosumab DS) y drogas antiangiogénicas ocasionan en el tejido óseo en aquellos pacientes que presentan como causa etiológica cáncer o discrasias óseas incluyen hipercalcemias malignas o ­si requieren el consumo de dicha droga a baja concentración­ como ser: osteoporosis, osteopenia, enfermedad de Paget, displasia fibrosa, Osteogénesis Imperfecta. (1) La presente actualización pretende relacionar el tratamiento odontológico con prescripción crónica y drogas antirresortivas, para lo cual American Association of Oral and Maxillofacial Surgeons AAOMS: define el concepto de Osteonecrosis Maxilar Asociada a drogas Antirresortivas (MRONJ) como: «Área ósea necrótica expuesta al medio bucal con más de ocho semanas de permanencia, en presencia de tratamiento crónico con bifosfonatos en ausencia de radioterapia en cabeza y cuello¼. La AAOMS estableció los siguientes grupos de acuerdo con sus características clínicas en 4 estadios (0, 1 ,2 y 3) de acuerdo con el aspecto clínico y radiológico de la lesión osteonecrótica. Estadío 0: lesión osteonecrótica sin evidencia de hueso necrótico en pacientes bajo consumo de drogas antirresortivas. Estadío 1: lesión osteonecrótica con signos clínicos y ausencia de sintomatología clínica. Estadío 2: lesión osteonecrótica con signo y sintomatología clínica evidente. Estadío 3: lesión osteonecrótica con signo y sintomatología evidente que compromete a estructuras nobles: fracturas patológicas, anestesia del nervio dentario inferior, comunicación buco-nasal, comunicación buco-sinusal, fístulas cutáneas (2) (AU)

It is known the favourable action which antiresorptive (Bisphosphonates BPs, Denosumab: DS) and Antiangiogenic drugs produce in bone tissue. High concentrations are primarily used as an effective treatment in the management of cancer-related disorders, including hypercalcemia of malignant. Besides, low concentrations are used for other metabolic bone diseases including Osteoporosis, Osteopenia, Paget's Disease, Fibrous Dysplasia, Imperfect Osteogenesis. (1) The update relate relationship between dentistry and chronic treatment with antiresorptive drugs. According to the American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ is defined as exposed or necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in association with current or previous BPs or DS therapy and with a lack of head and neck radiotherapy. AAOMS divided the MRONJ into 4 stages (0,1, 2 and 3) according to the clinical and radiological aspect of the osteonecrotic lesion: Stage 0: osteonecrotic lesion without sign-pathognomonic evidence of osteonecrosis. Stage 1: osteonecrotic lesion with clinical signs and absence of clinical symptoms. Stage 2: osteonecrotic lesion with sign and evident clinical symptoms. Stage 3: osteonecrotic lesion with signs and evident symptoms that involve noble structures: pathological fractures, anaesthesia of the lower dental nerve, oral-nasal communication, oral-sinus communication, skin fistulas (2) (AU)

Osteonecrosis de los maxilares asociada a medicamentos: revisión de la literatura y propuesta para la prevención y manejo / Osteonecrosis of the jaws

Medication-related osteonecrosis of the jaw is a disease where there is necrotic bone exposed or that can be explored by means of a fistula in the maxillofacial region. It has been associated with the use Biphosphonates and denosumab for osteoporosis. Although its etiology is unclear, it may be related to a decrease in bone turnover produced by these drugs, rendering the bone more prone to generate cell necrosis during invasive dental procedures, especially in the posterior region of the jaw. There is no consensus about the prevention and treatment of this condition. The aim of this paper is to present a review of the literature with the main characteristics of osteonecrosis of the jaws associated with drugs, together with a proposal for prevention and treatment for these patients.

The use of denosumab in giant cell tumors in the sacrum / O uso de denosumab em tumores de células gigantes no sacro / El uso de denosumab en el tumor de celulas gigantes en el sacro

ABSTRACT Giant Cell Tumor (GCT), a benign tumor with local aggression, corresponds to 5% of primary tumors. Fifteen percent of these are located in the sacrum. En bloc resection is an effective treatment, but when it cannot be performed, Denosumab may be indicated as an alternative treatment. The objectives of this work are: to justify the indication; determine the best dose and time of use; and recognize the need for post-treatment surgery. Methods A systematic search of clinical trials. Twenty-five articles were selected, ten of which met the inclusion criteria. The use of Denosumab is justified in advanced stages, with a dose of 120 mg administered subcutaneously, every 7 days in the first month and then maintained every 4 weeks, for 2.5 to 13 months. Adverse events are mild and can be observed in 84% of patients. With Denosumab, surgery may be less aggressive or even unnecessary. The bibliography justifies the indication of Denosumab in advanced stages of GCT, with a dose of 120 mg administered subcutaneously; there is no consensus as to the maintenance dose, which is a weekly dose in the first month and then every four weeks for 2.5 to 13 months. Complications are frequent but mild. Level of evidence III; Systematic review.

RESUMO O tumor de células gigantes (TCG), um tumor benigno com agressão local, corresponde a 5% dos tumores primários. Quinze por cento desses estão localizados no sacro. A ressecção em bloco é um tratamento eficaz, mas quando não pode ser realizada, o Denosumabe pode ser indicado como tratamento alternativo. Os objetivos desse estudo consistem em justificar a indicação; determinar a melhor dose e tempo de uso e reconhecer a necessidade de cirurgia pós-tratamento. Métodos Foi realizada uma busca sistemática de ensaios clínicos, sendo que foram selecionados 25 artigos, dos quais dez atenderam aos critérios de inclusão. O uso do Denosumabe é justificado em estágios avançados, com uma dose de 120 mg administrada por via subcutânea, a cada 7 dias no primeiro mês e, depois, mantida a cada 4 semanas, durante 2,5 a 13 meses. Os eventos adversos são leves e podem ser observados em 84% dos pacientes. Com o Denosumabe, a cirurgia pode ser menos agressiva ou nem necessária. A bibliografia justifica a indicação de Denosumabe em estágios avançados do TCG, com dose de 120 mg administrada por via subcutânea; não há consenso quanto à dose de manutenção, a qual é uma dose semanal no primeiro mês e depois a cada quatro semanas durante 2,5 a 13 meses. As complicações são frequentes, porém leves. Nível de evidência III; Revisão sistemática.

RESUMEN El tumor de células gigantes (TCG), un tumor benigno con agresión local, corresponde a 5% de los tumores primarios. Quince por ciento de éstos están localizados en el sacro. La resección en bloque es un tratamiento eficaz, pero cuando no puede ser realizada, el Denosumab puede ser indicado como tratamiento alternativo. Los objetivos de este estudio consisten en justificar la indicación, determinar la mejor dosis y tiempo de uso, y reconocer la necesidad de cirugía postratamiento. Métodos Fue realizada una búsqueda sistemática de ensayos clínicos, siendo que fueron seleccionados veinticinco artículos, de los cuales diez atendieron los criterios de inclusión. El uso de Denosumab está justificado en etapas avanzadas, con una dosis de 120 mg administrada por vía subcutánea, a cada 7 días en el primer mes y, después, mantenida a cada 4 semanas, durante 2,5 a 13 meses. Los eventos adversos son leves y pueden observarse en 84% de los pacientes. Con el Denosumab, la cirugía puede ser menos agresiva o ni necesaria. La bibliografía justifica la indicación de Denosumab en etapas avanzados de TCG, con dosis de 120 mg administrada por vía subcutánea; no hay consenso cuanto a la dosis de mantenimiento, la cual es una dosis semanal en el primer mes y después a cada cuatro semanas durante 2,5 a 13 meses. Las complicaciones son frecuentes, aunque leves. Nivel de evidencia III; Revisión Sistemática.

Impacto econômico da adoção de denosumabe em pacientes com metástases ósseas ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro / Economic impact of denosumab adoption in cancer patients with bone metastases or multiple myeloma from the Brazilian private healthcare system's perspective

Objetivo: Estimar o custo por evento relacionado ao esqueleto (ERE) e o impacto econômico anual da adoção de denosumabe em pacientes com metástases ósseas secundárias ao câncer de mama, próstata e outros tumores sólidos ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro. Métodos: Um modelo econômico foi desenvolvido para comparar os custos relacionados com denosumabe versus ácido zoledrônico na prevenção de EREs. O modelo incluiu os seguintes custos: medicamento, administração, monitoramento e manejo de ERE. O custo anual foi apresentado em reais (BRL) para 100 pacientes. Os custos do manejo de ERE [fratura vertebral (FV), fratura não vertebral (FNV), radiação óssea (RO), cirurgia óssea (CO) e compressão da medula espinhal (CME)] foram estimados a partir dos recursos e procedimentos coletados da revisão de literatura, bases de dados e painel Delphi. Dados coletados dos estudos clínicos randomizados relacionados com cada tipo de tumor na análise e de um estudo prospectivo observacional foram utilizados para estimar a eficácia clínica de denosumabe versus ácido zoledrônico. Resultados: O custo por cada tipo de ERE variou de BRL 27.246 a BRL 28.035 para FV, BRL 18.023 a BRL 18.811 para FNV, BRL 42.750 a BRL 43.538 para RO, BRL 18.023 a BRL 18.811 para CO e BRL 12.472 a BRL 13.260 para CME. A introdução de denosumabe foi estimada em economia anual por 100 pacientes de até BRL 1.072.043,14 para câncer de mama, BRL 1.212.822,79 para outros tumores sólidos, BRL 1.929.660,67 para câncer de próstata e BRL 77.965,07 para mieloma múltiplo. Conclusão: Esta análise sugere que EREs adicionam custos substanciais no manejo de pacientes com metástases ósseas. Dessa forma, o uso de denosumabe pode prevenir e retardar EREs em pacientes com câncer e pode possivelmente levar à redução do impacto econômico associado aos EREs sob a perspectiva dos pagadores de saúde privada brasileira.

Objective: To estimate the cost per SRE and annual economic impact of denosumab adoption in patients with bone metastases (BM) secondary to breast cancer, prostate cancer, other solid tumors or multiple myeloma from the Brazilian private healthcare system's perspective. Methods: An economic model was developed to compare the cost outcomes associated with denosumab instead of zoledronic acid for SRE prevention. The model included the following costs: drug, administration, monitoring and SRE management. Annual costs per 100 patients were reported in 2019 Brazilian currency (BRL). The SRE management costs (vertebral fracture (VF), non-vertebral fracture (NVF), radiation to bone (RB), surgery to bone (SB) and spinal cord compression (SCC)) were estimated from the resources and procedures collected from literature review, official database, and a Delphi panel. Data collected from randomized clinical trials related to each tumor type in the analysis and from a prospective observational study was used to estimate the clinical efficacy of denosumab vs zoledronic acid. Results: The cost per each type of SREs across all tumors ranged BRL 27,246 ­ BRL 28,035 for VF, BRL 18,023 ­ BRL 18,811 for NVF, BRL 42,750 ­ BRL 43,538 for RB, BRL 18,023 ­ BRL 18,811 for SB and BRL 12,472 ­ BRL 13,260 for SCC. The introduction of denosumab was estimated to result in annual savings per 100 patients of up to BRL 1,072,043.14 for breast cancer, BRL 1,212,822.79 for other solid tumors, BRL 1,929,660.67 for prostate cancer and BRL 77,965.07 for multiple myeloma. Conclusion: This analysis suggests that SREs add substantial costs to the management of patients with bone metastases. In this way, the use of denosumab would prevent and delay SREs in cancer patients and might possibly lead to reduce the economic burden associated with SREs, borne by Brazilian private healthcare payers.

Nuevos avances en el conocimiento de la historia natural de la displasia fibrosa / News advances in the knowledge of natural history of the fibrous dysplasia

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria, producida por una mutación activadora del gen GNAS, responsable de codificar la unidad a-estimuladora de la proteína G (Gsa). La presentación clínica de la enfermedad es muy variada, pues adopta desde formas asintomáticas hasta otras marcadamente sintomáticas. En los últimos años, el análisis exhaustivo de bases de datos de pacientes con DF ha permitido conocer más sobre su historia natural. En este artículo se revisa la información actualmente disponible sobre algunos aspectos que ayudarán al mejor enfoque clínico del paciente, como son: la utilidad clínica de los marcadores óseos, los factores pronósticos para el desarrollo de fracturas, la DF como condición predisponente para el desarrollo de tumores específicos, nuevas perspectivas sobre la fisiopatología del dolor óseo y nuevas estrategias terapéuticas. Un mayor conocimiento sobre la historia natural de esta enfermedad finalmente redundará en la mejor calidad de vida de los pacientes con DF. (AU)

Fibrous dysplasia (FD) is an infrequent, non-hereditary bone disease caused by a somatic mutation of the GNAS gene, responsible for encoding the a-subunit of the G-protein (Gsa). The clinical presentation of the disease varies greatly, with some patients being asymptomatic and others markedly symptomatic. The exhaustive analysis of the database from patients with FD has allowed to learn more about the natural history of this disease. This article reviews the current information available on the clinical utility of bone markers, the prognostic factors for the occurrence of fractures, the evidence supporting as a predisposing condition for the development of specific tumors, new perspectives on the pathophysiology of bone pain, and emerging therapeutic strategies. A greater understanding of the natural history of this disease will allow to make better medical decisions, which will ultimately contribute to improve FD patients' quality of life. (AU)

Effect of Osteoporosis Medication on Fracture Healing: An Evidence Based Review

A systematic search was conducted and relevant studies that evaluated the influence of osteoporosis medications (bisphosphonates [BPs], denosumab, selective estrogen receptor modulators [SERMs], recombinant human parathyroid hormone teriparatide [TPTD], and strontium ranelate [SrR]) on wrist, hip, and spine fracture healing, were selected. BPs administration did not influence fracture healing and clinical outcomes after distal radius fracture (DRF). Similar results were observed in hip fracture, but evidence is lacking for spine fracture. Denosumab did not delay the non-vertebral fractures healing in one well-designed study. No studies evaluated the effect of SERMs on fracture healing in humans. One study reported shorter fracture healing times in TPTD treated DRF patients, which was not clinically meaningful. In hip fracture, recent studies reported better pain and functional outcomes in TPTD treated patients. However, in spine fracture, recent studies found no significant differences in fracture stability between TPTD treated patients and controls. Evidence is lacking for SrR, but it did not influence wrist fracture healing in one study. In comparisons between TPTD and BPs, fracture healing and physical scores were not significantly different in hip fracture by 1 study. In spine fracture, controversy exists for the role of each medication to the fracture stability, but several studies reported that fracture site pain was better in TPTD treated patients than BPs treated patients. Considering no clinical data of negative fracture healing of the antiresorptive medication and the danger of subsequent fracture after initial osteoporotic fracture, there is no evidence to delay initiation of osteoporosis medications after fracture.