Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw / Conhecimento de dentistas brasileiros sobre a osteonecrose dos maxilares associada ao uso de bisfosfonatos

Osteonecrosis of the jaw associated with bisphosphonate use is a matter of utmost importance in clinical practice for the safe treatment of patients using this medication. Objective: The aim of this study was to evaluate the level of knowledge of dentists who carry out clinical practice about bisphosphonate-associated jaw osteonecrosis. Material and Methods: The methodology used in the present research consisted of a non-probability sampling approach for the selection of participants. To conduct the study, a questionnaire created on the Google Forms platform was sent via Direct on Instagram to the professionals who agreed to participate. The data were sent for analysis, using the frequency for each response, and the professionals were divided into subcategories according to their time of professional practice. Results: Participants were familiar with the purpose of the medication (65%) or had heard of it (34%); regarding the professionals' opinion on their knowledge and practice about bisphosphonate-related osteonecrosis a significant percentage (93.24%) responded positively regarding the existence of side effects resulting from the therapeutic use of bisphosphonates and 48.65% self-evaluated their level of knowledge on the subject as insufficient. Conclusion: The study reveals that almost all participating dentists have good knowledge about the effects caused by bisphosphonates, but some of them still do not feel specifically confident about the management and knowledge of jaw osteonecrosis (AU)

A osteonecrose dos maxilares associada ao uso de bisfosfonatos é um assunto de suma importância na prática clínica para o atendimento seguro dos pacientes que fazem uso terapêutico do medicamento. Objetivo: O objetivo deste trabalho foi avaliar o nível de conhecimento de cirurgiões dentistas que realizam atendimento clínico acerca da osteonecrose dos maxilares associada ao uso dos bisfosfonatos. Material e Métodos: A metodologia utilizada na presente pesquisa consistiu em uma abordagem de amostragem não probabilística para a seleção dos participantes. Para conduzir o estudo, enviamos um questionário criado na plataforma Google Forms via Direct no Instagram para os profissionais que concordaram em participar. Os dados foram enviados para análise, usando a frequência para cada resposta, sendo que os profissionais foram divididos em subcategorias por tempo de formação. Resultados: Os participantes estavam familiarizados com a finalidade do medicamento (65%) ou já haviam ouvido falar deles (34%); em relação à opinião dos profissionais sobre seu conhecimento e prática acerca da osteonecrose relacionada aos bisfosfonatos, observou-se que 48,65% autoavaliaram seu nível de conhecimento sobre o assunto como insuficiente e uma parcela expressiva (93,24%) respondeu positivamente em relação à existência de efeitos colaterais decorrentes ao uso terapêutico dos bisfosfonatos. Conclusão: O estudo revela que quase todos os dentistas participantes possuem um bom conhecimento acerca dos efeitos causados pelos bisfosfonatos, mas que parte deles ainda não se sentem seguros especificamente em relação ao manejo e conhecimento da osteonecrose dos maxilares (AU)

Long-term consequences of osteoporosis therapy with bisphosphonates

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study

Abstract Background Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. Methods In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. Results In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphospho-nate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. Conclusions The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms.@*METHODS@#Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH.@*RESULTS@#Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent.@*CONCLUSION@#At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Bushen Huoxue Prescription Regulates PINP and β-CTX in Treatment of Femoral Head Necrosis with Syndrome of Liver and Kidney Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.

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 inferior asociado a bifosfonatos / Lower jaw osteonecrosis associated with bisphosphonates / Osteonecrose do maxilar inferior associada a bisfosfonatos

Introducción: dada la alta prescripción de bifosfonatos, presentamos sus efectos adversos en la esfera odontológica, siendo una complicación poco frecuente, pero de difícil tratamiento. Sin necesidad de suspender el tratamiento, dado el importante beneficio en cuanto a la prevención de fractura por fragilidad. Estas fracturas causan una alta morbimortalidad en contraposición al bajo riesgo que conlleva la Osteonecrosis mandibular asociada a bifosfonatos. Objetivo: orientar al personal de salud que maneja estos fármacos y quien asiste dichas complicaciones a poseer conocimientos para la prevención de osteonecrosis. Identificar y diferenciar los pacientes con mayor riesgo, de acuerdo con la dosis de bifosfonatos y la frecuencia del tratamiento. Materiales y Método: se realizó una revisión bibliográfica en las siguientes fuentes: Scielo, Google académico, Medline/Pubmed, Biblioteca Virtual en Salud (Brasil), desde el año 2005 a la fecha, idiomas español, portugués e inglés. Los descriptores utilizados son bifosfonatos, mandíbula, maxilar, odontología, osteonecrosis, osteonecrosis de los maxilares asociada a bifosfonatos. Resultados: las últimas pautas de tratamiento fueron modificadas en 2014, por consenso de la Asociación Americana de cirugía Oral y Maxilofacial. La patogénesis de la osteonecrosis maxilar asociada a bifosfonatos no está completamente definida, aunque las publicaciones tratan de explicarla. El riesgo de desarrollarla por terapia oral es menor que por su administración vía intravenosa. Discusión: el médico que prescribe el antirresortivo debe conocer el estado de salud dental de su paciente y, en lo posible, remitirlo a examen con el odontólogo antes de iniciar la terapia con bifosfonatos.

Introduction: Given the high prescription of bisphosphonates, we present their adverse effects in the dental sphere, being an infrequent complication, but difficult to treat. There is no need to suspend treatment, given the important benefit in terms of prevention of fragility fractures. These fractures cause high morbimortality as opposed to the low risk associated with bisphosphonate-associated osteonecrosis of the jaw. Objective: To orient the health personnel who handle these drugs and who assist these complications to have knowledge for the prevention of osteonecrosis. To identify and differentiate patients at higher risk, according to the dose of bisphosphonates and frequency of treatment. Materials and Method: A literature review was performed in the following sources: Scielo, Google academic, Medline/Pubmed, Virtual Health Library (Brazil), from 2005 to date, Spanish, Portuguese and English languages. The descriptors used were bisphosphonates, mandible, maxilla, dentistry, osteonecrosis, osteonecrosis of the jaws associated with bisphosphonates. Results: The latest treatment guidelines were modified in 2014, by consensus of the American Association of Oral and Maxillofacial Surgery. The pathogenesis of bisphosphonate-associated maxillary osteonecrosis is not completely defined, although publications try to explain it. The risk of developing it by oral therapy is lower than by intravenous administration. Discussion: The physician who prescribes the antiresorptive drug should know the dental health status of his patient and, if possible, refer him for examination by a dentist before initiating bisphosphonate therapy.

Introdução: dada a alta prescrição de bisfosfonatos, apresentamos seus efeitos adversos na esfera odontológica, uma complicação rara, mas de difícil tratamento. Sem a necessidade de suspender o tratamento, dado o importante benefício em termos de prevenção de fraturas por fragilidade. Essas fraturas causam alta morbidade e mortalidade, em contraste com o baixo risco associado à osteonecrose da mandíbula associada aos bisfosfonatos. Objetivo: orientar a equipe de saúde que manipula esses medicamentos e que atende a essas complicações para que tenham conhecimento sobre a prevenção da osteonecrose. Identificar e diferenciar os pacientes de maior risco, de acordo com a dose de bisfosfonatos e a frequência do tratamento. Materiais e Método: foi realizada uma revisão da literatura nas seguintes fontes: Scielo, Google acadêmico, Medline/Pubmed, Biblioteca Virtual em Saúde (Brasil), de 2005 até a presente data, idiomas espanhol, português e inglês. Os descritores utilizados foram: bisfosfonatos, mandíbula, maxila, odontologia, osteonecrose, osteonecrose dos maxilares associada a bisfosfonatos. Resultados: as diretrizes de tratamento mais recentes foram modificadas em 2014, por consenso da Associação Americana de Cirurgia Oral e Maxilofacial. A patogênese da osteonecrose da mandíbula associada a bisfosfonatos não está totalmente definida, embora a literatura tente explicá-la. O risco de desenvolvê-la com a terapia oral é menor do que com a administração intravenosa. Discussão: o médico que prescreve o medicamento deve estar ciente do estado de saúde bucal do paciente e, se possível, encaminhar o paciente para ser examinado por um dentista antes de iniciar a terapia com bisfosfonatos.

Risk Factors of avascular Osteonecrosis of the Femoral Head in Children at the National ReferenceCenter for Sickle Cell Disease in Brazzaville, Congo

Introduction: The avascular osteonecrosis of the femoral head (AOFH) is a common complication of sickle cell disease (SCD). It exposes to lameness and sometimes to a very debilitating handicap. It is a source of desocialization, particularly in developing countries where prosthetic surgery remains inaccessible to the majority. This survey aimed to identify the risk of occurence AOFH. Materials and Methods: It was a case-control study carried between october 2017 and september 2021 at the National Reference Center for SCD « Antoinette Sassou Nguesso » in Brazzaville. It concerned 31 children with clinical and radiographic signs of AOFH. Clinical (age at diagnosis of SCD, frequency of vasoocclusive crises and hospitalization for vasoocclusive crises, number of blood transfusion) as well as hematological examination (blood count in the intercritical period) and hydroxyurea treatment were compared with those of 62 children with no clinical and radiographic signs of AOFH. The chi2 statistical test and the odds ratio were used for the comparison (P ˂ 0.05).Results: The sex ratio was 1.38 versus 0.93 (p = 0.50). The mean age of diagnostic of SCD was 3.76 ± 2.56 years versus 3.94 ± 2.01 years (p = 0.81). Logistic regression showed that SCD children with AOFH had a significantly higher rate of annual frequency of VOC (4.16 1.18 vs 2.91 1.68; P = 0.015), annual frequency of hospitalization for VOC (3.741.65 vs 1.451.28; P = 0.000) and number of blood transfusions (3.38 ± 2.69 vs 2.42 ± 2.32; P = 0.03).Conclusion: Emphasis should be placed on the prevention and early management of acute complications of SCD. The role of hydroxyurea should be clarified by further work.

Colocación de implantes en paciente con antecedentes de toma de bifosfonatos / Placement of implants in a patient with a history of bisphosphonates taken

El uso de bifosfonatos es un excelente tratamiento para pacientes con artritis reumatoide y enfermedades óseas, por ejemplo, osteoporosis. Se realiza un reporte de caso de paciente femenino, quien estuvo bajo consumo de este fármaco por prescripción de su médico para la prevención de artritis reumatoide postmenopausia. La paciente acude a consulta para la colocación de implantes en zona desdentada y comenta haber terminado el tratamiento de bifosfonatos hace un año. Se tomaron pruebas de diagnóstico y se realizó la colocación de implantes sin ninguna complicación. Sus citas de control fueron más frecuentes en cuatro meses, sobre todo por el detalle de consumo de bifosfonatos, pero en ninguna cita hubo algún detalle alarmante, la cicatrización iba en forma. Se dio de alta a la paciente después de sus citas periódicas y de asegurar su buena cicatrización a un implante bien situado (AU))

The use of bisphosphonates is an excellent treatment for patients with rheumatoid arthritis and bone diseases such as osteoporosis. Here is a case report of a female patient, who was under consumption of this drug by prescription of her doctor for the prevention of post-menopausal rheumatoid arthritis. The patient went to the consultation for the placement of implants in the edentulous area and comments having finished the bisphosphonate treatment one year ago. The diagnostic tests were taken, and the implant placement was performed well without any complications. The control appointments were more frequent in four months, especially due to the detail of bisphosphonate consumption, but in no appointment, there were any alarming details, the healing was in good shape. The patient discharged after her regular appointments and to ensure that she was healing well and that implant was well placed (AU)

Correlation of osteonecrosis rates in the surgical treatment of proximal humeral fractures according to the neer and hertel classifications / Correlação dos índices de osteonecrose no tratamento cirúrgico das fraturas do úmero proximal pelos critérios de neer e hertel

ABSTRACT Objective: To predict the risk of osteonecrosis (ON) according to the Neer and Hertel et al. classification for surgically treated proximal humeral fractures after at least one year of follow-up. Methods: This is a retrospective, cross-sectional, and observational cohort study. A total of 44 patients, 16 (36.36%) men and 28 (63.63%) women, with a mean age of 61.36 years, participated in this study. Lesions were categorized according to Neer and Hertel's classifications, considering the preoperative prognosis for ON. After at least a year of follow-up, patients were reassessed. Data were evaluated using IBM SPSS Statistics®. Results: A total of three patients (6.8%) developed osteonecrosis. Comparisons showed no statistically significant difference, but we observed a superior association of osteonecrosis for the Hertel classification than that of Neer. Conclusion: Both classifications showed a similar ability to identify patients at low risk of developing ON. New studies with a greater number of participants and sample homogeneity may intensify the value of the evaluation of clinical applicability and predictive capacity of the studied classifications with greater significance and correlation. Level of Evidence III, Case Control Study.

RESUMO Objetivo: Prognosticar o risco de osteonecrose (ON), segundo os critérios de Hertel et al. e a classificação de Neer, para fraturas do úmero proximal tratadas cirurgicamente após, pelo menos, um ano de seguimento. Métodos: Estudo de coorte retrospectiva, transversal e observacional. Foram encontrados 44 pacientes, sendo 16 (36,36%) do sexo masculino e 28 (63,63%) do feminino, com média de idade de 61,36 anos. As lesões foram categorizadas de acordo com os critérios de Neer e de Hertel et al., considerando o prognóstico pré-operatório para ON. Após pelo menos um ano de seguimento, os pacientes foram reavaliados. Os dados foram analisados por meio do programa IBM SPSS Statistics. Resultados: Três pacientes (6,8%) evoluíram com ON. As comparações não demonstraram diferença estatística significante, embora tenha sido possível observar associação superior para a classificação de Hertel et al. em comparação com a de Neer. Conclusão: As duas classificações apresentaram habilidade semelhante para identificar pacientes com baixo risco de desenvolver ON. Sugere-se a realização de novos estudos com maior número de participantes e homogeneidade da amostra para intensificar o valor da avaliação da aplicabilidade clínica e da capacidade preditiva das classificações estudadas, com aumento da significância e da correlação. Nível de Evidência III, Estudo Caso Controle.

Obesity influences the development of bisphosphonate-induced osteonecrosis in Wistar rats

Abstract Medication-related osteonecrosis of the jaw (MRONJ) is characterized by bone exposure for more than eight weeks in patients who have used or been treated with antiresorptive or antiangiogenic drugs, without a history of radiation therapy or metastatic diseases in the jaws. Obesity is associated with changes in periodontal tissues and oral microbiota that are linked to bone alterations. This study aimed to analyze the influence of obesity on the development of bisphosphonate-induced osteonecrosis. The experiment randomly and simply divided 24 male Wistar rats (Rattus norvegicus) into four groups: healthy, with osteonecrosis, obese, and obese with osteonecrosis (n=6 per group). Osteonecrosis was induced through weekly intraperitoneal injection for eight weeks at a dose of 250 µg/kg of zoledronic acid in a 4 mg/5 mL solution, combined with trauma (exodontia). Obesity was induced through a high glycaemic index diet. Each group was qualitatively and quantitatively evaluated regarding the development of models and pathological anatomy of the lesions. The results were expressed in mean percentage and standard deviation and statistically analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test, with a significance level of 5% (p<0.05) to establish differences found between the groups. Animals in the osteonecrosis group and the obese with osteonecrosis group presented larger necrosis areas (averages: 172.83±18,19 µm2 and 290.33±15,77 µm2, respectively) (p<0,0001). Bone sequestration, hepatic steatosis, and increased adipocyte size were observed in the obese group (average: 97.75±1.91 µm2) and in the obese with osteonecrosis group (average: 98.41±1.56 µm2), indicating greater tissue damage in these groups (p<0,0001). All parameters analyzed (through histological, morphometric, and murinometric analyses) increased for the obese and obese with osteonecrosis groups, suggesting a possible influence of obesity on the results. However, further studies are needed to confirm the role of obesity in the possible exacerbation of osteonecrosis and understand the underlying mechanisms.

Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

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)

Estudo in vivo do efeito da ozonioterapia como prevenção e/ou tratamento da osteonecrose dos maxilares induzida por medicamentos / In vivo study of the effect of ozone therapy as a prevention and/or treatment of druginduced osteonecrosis of the jaws

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,001), ZOL apresentou maior porosidade (p=0,03) e o espaçamento trabecular foi maior no grupo GOT quando comparado ao GOP (p< 0,05). A taxa de aposição mineral (MAR) dos grupos GOP foram maiores (21,46±14,12), seguida do grupo GOT (19,66± 13,23). GOT apresentou a maior média de %NBA (68,322±25,296), quando comparado ao grupo ZOL (p < 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)

Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.001), ZOL showed greater porosity (p=0.03) and the trabecular spacing was greater in the GOT group when compared to the GOP (p< 0 .05). The mineral apposition rate (MAR) of the GOP groups were higher (21,46±14,12), followed by the GOT group (19,66± 13,23). GOT had the highest average of %NBA (68.322±25.296), when compared to the ZOL group (p < 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)

Estudo in vivo do efeito da ozonioterapia como prevenção e/ou tratamento da osteonecrose dos maxilares induzida por medicamentos / In vivo study of the effect of ozone therapy as a prevention and/or treatment of druginduced osteonecrosis of the jaws

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)

Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)

Suspensión de antirresortivos en osteonecrosis asociada a medicamentos: revisión de la literatura / Suspension of antiresorptive drugs in medication-related osteonecrosis of the jaws: a review of the literature

La suspensión de antirresortivos en el contexto de cuadros de osteonecrosis asociada a medicamentos (ONAM) es controversial. Aunque la evidencia de ca-lidad al respecto es insuficiente, múltiples socieda-des profesionales y grupos de trabajo han sugerido emplear este recurso. Recientemente la Sociedad Americana de Cirujanos Orales y Maxilofaciales ha puesto en duda sus beneficios. En el presente estudio abordamos esta temática en dos situaciones clínicas diferentes. Por un lado, analizamos la suspensión de los antirresortivos en pacientes asintomáticos an-tes de llevar a cabo procedimientos invasivos en los maxilares para disminuir el riesgo de desarrollo de ONAM. Por otro lado, evaluamos la suspensión de los antirresortivos en pacientes con ONAM establecida para mejorar el pronóstico de la enfermedad (AU)

The suspension of antiresorptive drugs in the context of medication-related osteonecrosis of the jaws (MRONJ) is controversial. Despite the lack of quality evidence, several professional associations and working groups have made suggestions in using this resource. Recently the American Association of Oral and Maxillofacial Surgeons has questioned its benefits. In the present study we address this issue in two different clinical situations. On the one hand, we analyzed the suspension of antiresorptive agents in asymptomatic patients before carrying out invasive procedures in the jaws to reduce the risk of developing MRONJ. On the other hand, we evaluated the suspension of antiresorptive drugs in patients actually presenting MRONJ to improve the prognosis of the disease (AU)

Osteonecrosis of the jaws in patients under osteoporosis treatment: a nine-year experience report

ABSTRACT Objective: This study aimed to report the experience of medication-related osteonecrosis of the jaws (MRONJ) in osteoporotic patients for nine years, and their associated initiating factors. Materials and methods: The numbers of invasive oral procedures (IOP) (tooth extraction, dental implant placement, and periodontal procedures) and removable prostheses performed from January 2012 to January 2021 were obtained from the digital records of a large public dental center. There were an estimated 6,742 procedures performed in patients under osteoporosis treatment. Results: Two cases (0.03%) of MRONJ were registered in nine years amongst patients with osteoporosis who had dental treatment at the center. From the 1,568 tooth extractions, one patient (0.06%) developed MRONJ. There was also one case from the 2,139 removable prostheses delivered (0.05%). Conclusions: The prevalence of MRONJ associated with osteoporosis treatment was very low. The protocols adopted seem to be adequate for the prevention of this complication. The findings of this study reinforce the rare frequency of MRONJ associated with dental procedures in patients submitted to the pharmacological management of osteoporosis. An integral analysis of systemic risk factors and oral preventive strategies may be considered regularly in the dental treatment of these patients.

The Hertel classification can't predict the risk of humeral head osteonecrosis after osteosynthesis using an anterolateral approach

ABSTRACT Background: Proximal humeral fractures can progress to osteonecrosis of the humeral head. Hertel developed a binary classification system (12 subtypes) and demonstrated that some patterns have more risk to develop osteonecrosis. Hertel described the prevalence and the risk factors for Humeral head osteonecrosis after osteosynthesis using a Deltopectoral approach. Few studies have evaluated the prevalence and the capacity of Hertel's classification to predict Humeral Head osteonecrosis following osteosynthesis of proximal Humeral fractures through the anterolateral approach. The objectives of this study were to correlate osteonecrosis predictors established by the Hertel classification with the risk of developing osteonecrosis and its prevalence after osteosynthesis using the anterolateral approach. Methods: This was a retrospective study of patients who underwent osteosynthesis of proximal humerus fractures using an anterolateral approach. Patients were divided into two groups: high risk for necrosis (group 1) and low risk for necrosis (group 2) according to Hertel's criteria. The overall prevalence of osteonecrosis and the prevalence in each group were calculated. A radiological examination was performed in the true anteroposterior (Grashey), scapular, and axillary views, before and after the operation (minimum 1 year after surgery). A KaplanMeier curve was used to assess the pattern of the temporal evolution of osteonecrosis. The groups were compared using the Chi-square test or Fisher's exact test. The unpaired t-test (parametric variables - age) and the MannWhitney test (non-parametric time between trauma and surgery) were used. Results: In total, 39 patients were evaluated. The postoperative follow-up time was 14.5 ± 3.3 months. The time to onset of necrosis was 14.1 ± 3.9 months. Sex, age, and time between trauma and surgery did not influence the risk of necrosis. Type 2, 9, 10, 11, and 12, or fractures with posteromedial head extension less than or equal to 8 mm, or diaphysis deviation greater than 2 mm, as well as grouping did not influence the risk for osteonecrosis. Conclusions: Hertel's criteria were not able to predict the development of osteonecrosis after osteosynthesis of proximal humerus fractures performed through the anterolateral approach. The total prevalence of osteonecrosis was 17.9% with a tendency toward an increased incidence after 1 year of surgical treatment.

Visual and quantitative assessment of the effectiveness of non-vascularized bone grafting in osteonecrosis of the femoral head via CT-based radiomics and clinical data / 中国修复重建外科杂志

OBJECTIVE@#To investigate the value of CT-based radiomics and clinical data in predicting the efficacy of non-vascularized bone grafting (NVBG) in hip preservation, and to construct a visual, quantifiable, and effective method for decision-making of hip preservation.@*METHODS@#Between June 2009 and June 2019, 153 patients (182 hips) with osteonecrosis of the femoral head (ONFH) who underwent NVBG for hip preservation were included, and the training and testing sets were divided in a 7∶3 ratio to define hip preservation success or failure according to the 3-year postoperative follow-up. The radiomic features of the region of interest in the CT images were extracted, and the radiomics-scores were calculated by the linear weighting and coefficients of the radiomic features after dimensionality reduction. The clinical predictors were screened using univariate and multivariate Cox regression analysis. The radiomics model, clinical model, and clinical-radiomics (C-R) model were constructed respectively. Their predictive performance for the efficacy of hip preservation was compared in the training and testing sets, with evaluation indexes including area under the curve, C-Index, sensitivity, specificity, and calibration curve, etc. The best model was visualised using nomogram, and its clinical utility was assessed by decision curves.@*RESULTS@#At the 3-year postoperative follow-up, the cumulative survival rate of hip preservation was 70.33%. Continued exposure to risk factors postoperative and Japanese Investigation Committee (JIC) staging were clinical predictors of the efficacy of hip preservation, and 13 radiomic features derived from least absolute shrinkage and selection operator downscaling were used to calculate Rad-scores. The C-R model outperformed both the clinical and radiomics models in predicting the efficacy of hip preservation 1, 2, 3 years postoperative in both the training and testing sets ( P<0.05), with good agreement between the predicted and observed values. A nomogram constructed based on the C-R model showed that patients with lower Rad-scores, no further postoperative exposure to risk factors, and B or C1 types of JIC staging had a higher probability of femoral survival at 1, 2, 3 years postoperatively. The decision curve analysis showed that the C-R model had a higher total net benefit than both the clinical and radiomics models with a single predictor, and it could bring more net benefit to patients within a larger probability threshold.@*CONCLUSION@#The prediction model and nomogram constructed by CT-based radiomics combined with clinical data is a visual, quantifiable, and effective method for decision-making of hip preservation, which can predict the efficacy of NVBG before surgery and has a high value of clinical application.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.