Medication-related osteonecrosis of the jaw: the radiologist's role.

In recent decades, the dreaded adverse effect of bisphosphonates, osteonecrosis of the jaw, has been widely reported and described in detail. Osteonecrosis of the jaw consists of the destruction of part of the maxilla as a consequence of these antiresorptive drugs. In recent years, new drugs that can also cause osteonecrosis of the jaw (e.g., some monoclonal antibodies or antiangiogenic drugs) have come on the market. For this reason, the term "bisphosphonate-related osteonecrosis of the jaw" has been replaced with "medication-related osteonecrosis of the jaw (MRONJ). This review aims to describe the radiologic characteristics of MRONJ that, although nonspecific, radiologists need to recognize in the appropriate clinical context.

Effectiveness and safety of bisphosphonates therapy in secondary osteoporosis in children.

INTRODUCTION: There are few studies on effectiveness and safety of bisphosphonate therapy in secondary osteoporosis in children. The aim of this research was to analyse effectiveness and safety of bisphosphonates in secondary osteoporosis in children. PATIENTS AND METHODS: Multicentre retrospective study in patients younger than 18 suffering from secondary osteoporosis and who have received bisphosphonates. Clinical data were recorded. Bone mineral density (BMD) was assessed in terms of BMD Z-score in lumbar spine (ZBMDls) measured by dual-energy X-ray absorptiometry (DXA). Effectiveness was valued at changes in ZBMDls one and two years after the onset of bisphosphonates and at the decrese in the number of fractures a year. Adverse events reported were recorded. Descriptive and bivariant analysis was performed. RESULTS: 32 patients were recruited. ZBMDls increased one year after the onset of treatment ((-2.46 ± 0.96) vs. (-1.54 ± 1.38); p < .001). Fractures a year dicreased significantly (1 (1-2) vs. 0 (0-0.61); p < .001). ZBMDls increase was higher in patients who were able to walk (1.88 ± 0.72 vs. 0.55 ± 0.82; p = .07) and correlated positively with body mass index (BMI)- for- age percentile (rho: 0.564; p < .001). The decrease in the number of fractures a year was higher in patients with lower initial fracture rate (rho: -0,47; p = .006) and with higher initial ZBMDls (rho: -0.47; p = .07). 10 adverse events were reported in 7 patients (22%), all of them intravenous bisphosphonates related. No association was found between adverse events and studied variables. CONCLUSIONS: Bisphosphonates are effective in secondary osteoporosis in children. Response seems to be better in patients who are able to walk, well-nourished and in the early stages of the disease. Adverse events were frequent but mild.

Effect of antiresorptive and bone forming treatments in bone erosions in rheumatoid arthritis. / Efecto del tratamiento antirresortivo y osteoformador en las erosiones óseas en la artritis reumatoide.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can cause joint destruction and marked disability. Early treatment with disease-modifying drugs, including biological therapy, is the principal treatment to prevent the structural damage associated with this entity. Some studies have indicated that concomitant treatment with antiresorptives, such as bisphosphonates or denosumab, could prevent erosive lesions in this process, and it has even been suggested that treatment with a bone forming agent, such as teriparatide, could revert previously established erosive lesions. In this article we review the evidence available on the efficacy of treatment with antiresorptives and bone forming agents in the prevention and/or treatment of bone erosions associated with RA.

[Generalized arterial calcification in childhood: A case report]. / Calcificación arterial generalizada idiopática de la infancia: a propósito de un caso.

INTRODUCTION: Arterial calcification of infancy is a rare autosomal recessive genetic disorder with extremely poor prognosis characterized by extensive calcification of internal elastic lamina and thickened of intimal tissue of large and medium sized arteries. CASE REPORT: We present the case of a newborn necropsy with hydrops and widespread cyanosis. The internal examination revealed heart enlargement due to occlusive calcification of the arteries. DISCUSSION: The aim of the present report is to provide a correlation of clinical and pathological features. An update of genetic diagnosis is provided.

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)

Osteoporosis, bone mineral density and CKD-MBD (II): Therapeutic implications. / Osteoporosis, densidad mineral ósea y complejo CKD-MBD (II): implicaciones terapéuticas.

Osteoporosis (OP) and chronic kidney disease (CKD) both independently affect bone health. A significant number of patients with CKD have decreased bone mineral density (BMD), are at high risk of fragility fractures and have an increased morbidity and mortality risk. With an ageing population, these observations are not only dependent on "renal osteodystrophy" but also on the associated OP. As BMD predicts incident fractures in CKD patients (partI), we now aim to analyse the potential therapeutic consequences. Post-hoc analyses of randomised studies have shown that the efficacy of drugs such as alendronate, risedronate, raloxifene, teriparatide and denosumab is similar to that of the general population in patients with a mild/moderate decline in their glomerular filtration rate (especially CKD-3). These studies have some flaws however, as they included mostly "healthy" women with no known diagnosis of CKD and generally with normal lab test results. Nevertheless, there are also some positive preliminary data in more advanced stages (CKD-4), even though in CKD-5D they are more limited. Therefore, at least in the absence of significant mineral metabolism disorders (i.e. severe hyperparathyroidism), the potential benefit of these drugs should be considered in patients with a high or very high fracture risk. It is an important change that the new guidelines do not make it a requirement to first perform a bone biopsy and that the risk/benefit ratio of these drugs may be justified. However, we must also be aware that most studies are not consistent and the level of evidence is low. Consequently, any pharmacological intervention (risk/benefit) should be prudent and individualised.

O uso de bisfosfonatos causa implicações na movimentação dentária ortodôntica? / Does the use of biophosphonates cause implications on the orthodontic tooth movement?

Bisfosfonatos são medicamentos que reduzem a reabsorção óssea, inibindo a atividade enzimática dos osteoclastos. Por essa razão, são amplamente utilizados no tratamento de várias doenças, como a osteoporose. Durante o tratamento ortodôntico, a aplicação de forças compressivas no dente promove a reabsorção e remodelação óssea, permitindo sua movimentação. Vários estudos in vivo observaram a diminuição da movimentação ortodôntica por bisfosfonatos, tornando o tema relevante devido à crescente demanda de tratamento ortodôntico em idosos ­ principais usuários dessa droga. Assim sendo, o objetivo deste trabalho é avaliar evidências do uso de bisfosfonatos no decorrer do tratamento ortodôntico e, mais especificamente, examinar seus efeitos na movimentação ortodôntica através de mensurações clínico-laboratoriais. Para isso, foi realizada uma revisão sistematizada na base de dados Pubmed através dos descritores Ortodontia e Bisfosfonatos. Buscou-se estudos em inglês entre 2015 e 2020. De 39 artigos compatíveis à proposta, 8 artigos passaram pelos critérios de inclusão e exclusão. Desses, a maioria dos autores é categórica em se referir ao uso de bisfosfonatos como um fator relevante para índices inferiores de movimentação. Porém, tais dados devem ser vistos com cautela, pois os métodos utilizados são variados, havendo uma grande heterogeneidade. Ademais, pequenas amostras e tempo curto dos experimentos não permitem uma generalização para pacientes de rotina. Como conclusão temos que a administração de bisfosfonatos associada à movimentação ortodôntica aparenta provocar uma duração prolongada no tratamento devido, fundamentalmente, aos índices inferiores de movimentação dentária planejada. Entretanto, os fatores específicos para tal não estão plenamente explicados.

Bisphosphonates are drugs that provide bone resorption by inhibiting the enzyme activity of osteoclasts. For this reason, they are widely used in the treatment of various diseases, such as osteoporosis. During orthodontic treatment, the application of compressive forces on the tooth promotes bone resorption and remodeling, allowing its movement. Several in vivo studies observed a decrease in orthodontic movement caused by bisphosphonates, making the topic relevant due to the growing demand for orthodontic treatment in the elderly - the main users of this drug. Therefore, the aim of this study is to evaluate evidence of the use of bisphosphonates during orthodontic treatment and, more specifically, to examine their effects on orthodontic movement through clinical and laboratory measurements. For this, a systematized review was performed in the Pubmed database using the descriptors Orthodontics and Bisphosphonates. Studies in English between 2015 and 2020 were sought. Of 39 articles compatible with the proposal, 8 articles passed the inclusion and exclusion criteria. Most authors are categorical in referring to the use of bisphosphonates as a relevant factor for lower movement rates. However, such data must be viewed with caution, as the methods used are sundry, with great heterogeneity. Furthermore, small administrations and short experimental times do not allow generalization to routine patients. In conclusion, the administration of bisphosphonates associated with orthodontic movement seems to cause a prolonged duration of treatment, fundamentally due to the lower rates of planned tooth movement. However, the specific factors for this are not fully explained.

Impacto do uso sistêmico de estatinas e de bisfosfonatos nos tecidos periodontais: revisão narrativa / Impact of the systemic use of statins and bisphosphonates in the periodontal tissues: narrative review

Introdução: A literatura tem apontado uma possível relação entre diversas condições sistêmicas e as doenças periodontais. Dentro das doenças sistêmicas que podem gerar o uso crônico de medicamentos, com potencial associação com as doenças periodontais, destacam-se a hipercolesterolemia e o uso de estatinas; e as doenças do metabolismo ósseo e o uso de bisfosfonatos. Objetivo: Dessa maneira, o presente estudo objetivou revisar a literatura sobre o efeito das estatinas e dos bisfosfonatos nos parâmetros clínicos e radiográficos periodontais de indivíduos adultos. Resultados: Apenas estudos observacionais em humanos foram incluídos. Um estudo mostrou que, em pacientes que apresentam doença periodontal e usam estatina, houve 37% menos bolsas periodontais (profundidade de sondagem ≥4mm) quando comparadas aos que não utilizam a medicação, além de apresentarem menor índice de carga inflamatória e menor perda de inserção clínica. Em relação aos bisfosfonatos em indivíduos com doenças que envolvem o metabolismo ósseo, sugere-se que a utilização do fármaco tem obtido resultados positivos nos parâmetros periodontais, como menores sinais clínicos de inflamação gengival, menor profundidade de sondagem, menor perda de inserção clínica e maior nível de osso alveolar, quando comparados aos que nunca realizam essa terapia. Conclusão: Dessa forma, as estatinas e os bisfosfonatos apresentam efeitos promissores, em pacientes sob tratamento para suas respectivas condições sistêmicas, na melhoria dos parâmetros periodontais, porém é importante salientar que são necessários mais estudos sobre o assunto para melhor entender os reais efeitos a longo prazo do uso desses fármacos.(AU)

Introduction: The literature showed a possible relationship between several systemic conditions and periodontal diseases. Within the systemic diseases that can generate the chronic use of these drugs, potentially related with periodontal diseases, it may be cited the hypercholesterolemia and the use of statins; and bone metabolism diseases and the use of bisphosphonates. Objective: In this sense, the present study aimed to review the literature about the effect of statins and bisphosphonates in the periodontal parameters of adults individuals. Results: Only observational studies in humans were included. A study showed that, in patients with periodontal disease and users of statins, there 37% fewer periodontal pockets (probing depth ≥4mm) when compared to those who do not use the medication, as well as having a lower rate of inflammatory burden and less loss of clinical insertion. Regarding the bisphosphonates in individuals diagnosed with diseases involving bone metabolism, it was suggested that the use of the drug has obtained positive results in periodontal parameters, such as a greater absence of plaque, less clinical signs of gingival inflammation, less probing depth, lower level of clinical insertion and higher level of alveolar bone when compared to those who never undergo this therapy. Conclusion: Thus, statins and bisphosphonates have promising effects in patients under treatment for their respective systemic condition in improving periodontal parameters, but it is important to emphasize that further studies on the subject are needed to better understand the long-term effects of the use of these drugs.(AU)

Cuidado em saúde bucal para pacientes que utilizam antirreabsortivos ósseos / Oral health care for patients under antiresorptive therapy

O cenário odontológico tem apresentado diversos casos de infecção odontogênica, inclusive com óbitos. Em linha com esses fatos, observa-se o aumento na prescrição de antirreabsortivos ósseos em Serviços de Saúde particulares e do SUS (Sistema Único de Saúde). Os bisfosfonatos injetáveis têm ação comprovadamente benéfica para o controle de metástases ósseas. Contudo, aponta-se a osteonecrose avascular no complexo bucomaxilofacial como um efeito adverso importante. Este tipo de alteração também foi reportado mediante o uso de antiangiogênicos e imunomoduladores. Esta revisão de literatura teve por objetivo delinear um protocolo que respalde a atuação dos Cirurgiões Dentistas Clínicos Gerais nas Unidades de Atenção Primária à Saúde do Município de Campinas-SP, diante da utilização frequente de antirreabsortivos ósseos e uma demanda reprimida por cuidados em Saúde Bucal que se apresenta com a retomada integral das atividades após o pico da pandemia de COVID-19. Com base no conhecimento científico sobre a osteonecrose associada a medicamentos, sugere-se que as equipes das Unidades de Atenção Primária à Saúde atuem de modo preventivo, proporcionando cuidado em Saúde Bucal preferencialmente antes do início do tratamento com antirreabsortivos. No entanto, para pacientes que já estão sob esta terapia e necessitam de intervenções odontológicas invasivas, recomenda-se uma abordagem multidisciplinar, entre Cirurgiões Dentistas da Atenção Primária e da Atenção Secundária, visando ao tratamento de possíveis complicações das intervenções invasivas de urgência. Ademais, pacientes sob uso de antirreabsortivos ósseos requerem monitoramento a longo prazo, para se evitar a necessidade de procedimentos odontológicos invasivos ou mesmo diagnosticar precocemente casos de osteonecrose.

The dental scenario has shown many cases of odontogenic infection, including some that ended with death. Along with these facts, there has been an increasing prescription of antiresorptive drugs, both in private and Unified Health System (SUS) Health Services. Injectable bisphosphonates have well-established beneficial action for controlling osseous metastasis. Nevertheless, avascular osteonecrosis of the bucomaxillofacial complex has been pointed out as an important side effect. Such a condition has also been reported under treatment with antiangiogenic drugs and immunological checkpoints inhibitors. This literature review aimed at offering a protocol to support the clinical practice of general dental practitioners in Primary Health Care Units from Campinas-SP Municipality, in face of frequent use of antiresorptive drugs and a repressed demand for oral health care, which takes place with thorough return of activities after COVID-19 pandemic peak. On the basis of scientific knowledge about medication-related osteonecrosis, it may be suggested that staffs in Primary Health Care Units adopt preventive measures, providing oral health care preferably before the beginning of antiresorptive therapy. However, for patients who are already under antiresorptive therapy and need invasive oral interventions, it is recommended a multidisciplinary approach, comprising Dentists from Primary and Secondary Health Care Units, trying to intercept possible complications of urgent invasive oral interventions. Besides, patients under use of antiresorptive medications require long-term follow-up, to avoid the need for invasive oral procedures or to make early diagnosis of osteonecrosis.

Knowledge of dentistry students on bisphosphonate-related osteonecrosis of the jaw / Conhecimento de alunos do curso de Odontologia sobre osteonecrose dos maxilares relacionada ao uso de bisfosfonatos

Objective: Bisphosphonates are anti-resorptive drugs used in the control and treatment of calcium and bone metabolism disorders. Despite their high clinical efficacy, these drugs have been associated with bisphosphonate-related osteonecrosis of the jaw. The goal of this study is to evaluate the knowledge of final year undergraduate dentistry students on bisphosphonate-related osteonecrosis of the jaw. Material and Methods: A sample of 100 students from private institutions in the state of São Paulo was invited to complete a questionnaire relating to bisphosphonates and the risk factors associated with the development of osteonecrosis of the jaws. Results: 66% of the students did not recognize any bisphosphonate (p=0.0019) and 79% did not recognize their trademark names (p<0.0001). 60% of the students recognized osteonecrosis of the jaws as a side effect of bisphosphonates (p<0.0001) and 56% identified at least one risk factor associated with the drug that may contribute to the side effect (p<0.0001). 66% of the students stated that their course did not provide any lectures on the topic (p<0.0001). Conclusion: The knowledge of dentistry students about bisphosphonates and bisphosphonate-related osteonecrosis of the jaw is variable. This may be related to an inadequate discussion of this topic during their undergraduate studies(AU)

Objetivo: Os bisfosfonatos são medicamentos antirreabsortivos utilizados no controle e tratamento de desordens do cálcio e do metabolismo ósseo. Apesar da elevada eficácia clínica, a terapia com estes medicamentos tem sido associada a uma importante complicação denominada de osteonecrose dos maxilares relacionada ao uso de bisfosfonatos. O objetivo deste estudo é avaliar conhecimento sobre a osteonecrose dos maxilares relacionada ao uso de bisfosfonatos entre os alunos do último ano do curso de graduação de Odontologia. Material e Métodos: Uma amostra de 100 alunos de instituições privadas do estado de São Paulo foi convidada a responder um questionário sobre as principais informações dos bisfosfonatos e fatores de risco associados com o desenvolvimento da osteonecrose dos maxilares. Resultados: Os 100 questionários foram respondidos: 66% dos estudantes não reconheceram algum bisfosfonato (p=0,0019), 79% não reconheceram seus nomes de marcas comerciais (p<0,0001); 60% dos alunos reconheceram a osteonecrose dos maxilares como um efeito colateral dos bisfosfonatos (p<0,0001) e 56% apontaram pelo menos um fator de risco associado com o medicamento que pode causar o desenvolvimento do efeito colateral (p<0,0001); 66% dos estudantes afirmaram que o curso não forneceu alguma aula abordando esta temática (p<0.0001). Conclusão: O grau de conhecimento dos alunos de Odontologia sobre bisfosfonatos e osteonecrose dos maxilares relacionada ao uso de bisfosfonatos é variável e está relacionado com a pouca discussão deste tema durante a graduação(AU)

Treatment of postmenopausal osteoporosis: a literature-based algorithm for use in the public health care system.

Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.

Androgen deprivation in prostate cancer and the long-term risk of fracture. / Deprivación andrógenica en cáncer de próstata y riesgo de fractura a largo plazo.

OBJECTIVES: To determine the rate of bone mass loss and the risk of fracture induced by androgen deprivation therapy in patients with prostate cancer. MATERIAL AND METHODS: Prospective study in 2 phases. In the first phase, demographic variables, FRAX®, bone mineral density and clinical fractures were collected, before starting the therapy and up to 1 year after ending the therapy. In the second phase, we conducted a telephone interview a mean of 8.5 years after the start of the study to assess new fractures. RESULTS: We included 150 patients with a mean age of 67 years and a mean therapy duration of 24 months. Before starting the treatment, 62 patients (41%) showed osteoporosis or low bone mass in the densitometry. After the first year of treatment, the bone mineral density decreased a mean of 3.7% and 2.1% in the lumbar spine and femoral neck, respectively. At the end of the second and third year, the loss rate was lower. During the first phase of the study, 4 patients (2.7%) experienced a fracture. In the telephone interviews with 80 patients (53%), only 1 had experienced a fracture. CONCLUSIONS: In the patients with prostate cancer and androgen deprivation therapy, greater bone loss occurred during the first year. When the treatment did not exceed 2 years, the absolute risk of fracture was low, and clinical fractures were uncommon in the short and long term.

[Deprescribing long-term treatments with bisphosphonates for osteoporosis in primary care in the Basque Country (Spain)]. / Desprescripción de tratamientos de larga duración con bisfosfonatos para la osteoporosis en atención primaria en el País Vasco.

OBJECTIVE: To evaluate the impact of a multifactorial intervention to promote bisphosphonate deprescription after over 5 years of use (BF5y) in a health care organisation (HCO) in Gipuzkoa (Spain) and to compare it with the standard intervention in other HCOs in the Basque Health Service-Osakidetza. METHODS: An 8-month follow-up study (results from before and after) to assess the impact of two interventions. All patients from Osakidetza receiving BF5y treatment (electronic prescription) in July 2013 were included. The standard intervention (9 HCOs) consisted of mailing a consensus statement on BF5y deprescribing and facilitating patient identifiers with BF5y prescription for review by the primary care physician. The multifactorial intervention (Gipuzkoa) also included a local consensus with leading specialists and training sessions in health centres. RESULTS: 18,725 patients were included; 94.7% were women. Standard intervention deprescribing rates ranged from 26.4% (Bilbao) to 49.4% (Araba), being 37.2% overall. The multifactorial intervention deprescribing rate was 44.6%, 7.4% (p <0.0001; 95% confidence interval [95%CI]: 5.4-9.4) higher than standard intervention. Changes to other treatments were less common with the multifactorial intervention, with a difference of 3.7% (p <0.0001; 95%CI: -2.2 to -5.2). CONCLUSIONS: Standard and multifactorial interventions are very effective in reducing unnecessary treatments with bisphosphonates. The multifactorial intervention is more effective than the standard one, although more complex to implement.

Intervention to improve awareness of the risk factors for osteonecrosis of the jaw in patients under treatment with bisphosponates. Randomised clinical trial. / Intervención para la mejora del conocimiento de los factores de riesgo para el desarrollo de osteonecrosis maxilar en pacientes a tratamiento con bisfosfonatos. Ensayo clínico aleatorizado.

PURPOSE: To evaluate the effectiveness of a health education programme on knowledge and reduction of the risk factors for bisphosphonate-related osteonecrosis of the jaw. METHODS: An experimental study control group without intervention was performed with 60 subjects who had started treatment with bisphosphonates in the University Hospital of León from October to December 2014. Patients in the experimental group received a structured education intervention in two sessions. The data was collected from a heteroadministered questionnaire at the beginning and at the end of the study period for both groups. RESULTS: The educational intervention designed showed a significantly increased adherence to healthy behaviours related to oral hygiene such as mechanical control of plaque and the use of clorhexidine prior to invasive oral procedures. All subjects reported that they had not been advised to maintain a good level of oral health before starting treatment. After the intervention high percentages of recognition of early diagnostic measures starting from a baseline total ignorance of them were determined. No conclusive information about the use of removable dental prostheses, toxic habits or maintaining proper metabolic control in patients with diabetes mellitus was observed. CONCLUSIONS: Improving adherence to healthy behaviours related to oral health following the intervention, as well as their contribution to the early identification of warning signs of jaw osteonecrosis, stresses the importance of the use of health education as a tool in routine clinical practice.

Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients / Fatores de risco para osteonecrose dos maxilares relacionada à medicação e níveis salivares de IL-6 em pacientes com câncer

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient's quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

Resumo Introdução A osteonecrose dos maxilares relacionada à medicação é uma complicação grave da terapia antirreabsortiva e antiangiogênica, com opção de tratamento limitada e grande impacto na qualidade de vida do paciente. Objetivo Avaliar os fatores de risco associados à osteonecrose dos maxilares relacionada à medicação em pacientes oncológicos em tratamento com bifosfonato Além disso, os níveis salivares de interleucina-6 (IL-6) foram medidos para investigar sua associação com a gravidade e o risco de osteonecrose dos maxilares relacionada à medicação. Método Estudo caso-controle com 74 pacientes com metástases ósseas de tumores sólidos e mieloma múltiplo. Os pacientes foram divididos em três grupos: 1) em tratamento por bifosfonato com osteonecrose dos maxilares relacionada à medicação; 2) submetidos ao bifosfonato sem osteonecrose dos maxilares relacionada à medicação; e 3) pré-tratamento de bifosfonato. Os dados demográficos e médicos dos pacientes foram coletados para avaliar o risco. A avaliação clínica foi feita para diagnosticar osteonecrose dos maxilares relacionada à medicação e a saliva não estimulada foi coletada para quantificação da IL-6. Resultados Observou-se que os pacientes diagnosticados com osteonecrose dos maxilares relacionada à medicação foram submetidos a maior número de doses de bifosfonato (p = 0,001) e protocolo de infusão mensal (p = 0,044; OR = 7,75). Pacientes que não tiveram acompanhamento de rotina com dentistas especializados durante a terapia com bifosfonato e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação (p = 0,019; OR = 8,25 e p = 0,031; OR = 9,37, respectivamente). O grupo 1 apresentou maior frequência de tratamento com quimioterapia e corticosteroides concomitantes ao bifosfonato e procedimentos odontológicos cirúrgicos (p = 0,129). Os níveis salivares de IL-6 não apresentaram diferença estatisticamente significante entre os grupos (p = 0,571) ou associação com a gravidade do osteonecrose dos maxilares relacionada à medicação (p = 0,923). Conclusão Maior número de ciclos de bifosfonato, protocolo de infusão mensal, ausência de acompanhamento odontológico para manutenção da saúde bucal e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação. O acompanhamento odontológico especializado durante o tratamento demonstrou ser importante na prevenção dessa complicação.

Fracturas atípicas de fémur, un evento adverso infrecuente de los bisfosfonatos en oncología. Reporte de caso / Atypical femur fractures, a rare adverse event of bisphosphonates in oncology: Case report

Resumen Los bisfosfonatos constituyen uno de los pilares fundamentales en el manejo de la morbilidad ósea de los pacientes con varios tipos de tumores sólidos (1, 3). Sin embargo, a pesar de la experiencia que tenemos por su uso desde hace décadas, existen eventos adversos como las fracturas atípicas (FA) que por su baja frecuencia pueden pasar desapercibidas y no recibir un manejo adecuado. Existen pocos reportes en la literatura de FA en el manejo de pacientes con cáncer. Se presenta un caso en el cual una paciente con un tumor metacrónico de mama con metástasis ósea al debut, actualmente en remisión, presenta una FA de fémur tras recibir bisfosfonatos durante 8 años.

Abstract Bisphosphonates are one of the fundamental pillars in the treatment of bone morbidities in patients with different types of solid tumors.1-3 However, despite the experience that we have accumulated during decades, there are adverse events such as atypical fractures (AF) that due to their low frequency can go unnoticed and might not receive adequate management. There are few reports in the literature about AF in cancer treatments. We present a case of a patient with metachronous breast cancer and bone metastases at initial diagnosis, currently in remission, who presents AF of the femur after receiving bisphosphonates for 8 years.

Impact of Antiresorptive Agents on Maxillary Bones: a Narrative Literature Review / Impacto dos Agentes Antirreabsortivos nos Ossos Maxilares: uma Revisão de Literatura narrativa

Abstract Antiresorptive drugs operate in the bone metabolism modulation and are widely used in the treatment of bone metastases and bone losses related to hormonal deficiency. Although this therapy shows satisfactory results, there are adverse effects associated with its use, such as osteonecrosis of the jaws. Medication-related osteonecrosis of the jaws (MRONJ) is, therefore, a serious and challenging condition with important implications in dentistry. The aim was to conduct a narrative literature review on anti-resorptive drugs and their latest repercussions on the maxillary bones. The review was carried out through a bibliographic search using Decs/Mesh descriptors of interest, in Portuguese and English, in the PubMed, Virtual Health Library (VHL) and Scielo databases. After applying the inclusion and exclusion criteria, a total of 33 studies were selected for analysis. It can be noticed that therapy with anti-resorptive agents is complex, especially in dental practice, since MRONJ is a complication that is difficult to manage. Regarding the therapeutic options, these are divided into conservative, surgical or adjuvant therapy, however, there are no protocols in the literature, and there is no consistency regarding the indication of the suspension of the drug administration - "Drug Holiday". Thus, it is important that the multidisciplinary team seeks strategies that minimize complications and promote control over the use of these drugs. In addition, there is a need for investigations that contribute with guidelines for the management and control of adverse effects resulting from therapy with antiresorptive drugs. (AU)

Resumo As drogas antirreabsortivas atuam na modulação do metabolismo ósseo e são indicadas para o tratamento de metástases ósseas e perdas ósseas relacionadas à deficiência hormonal. Ainda que esta terapia apresente resultados satisfatórios, observam-se efeitos adversos associados ao seu uso, como a osteonecrose dos maxilares. A osteonecrose dos maxilares associada ao uso de medicamentos (OMAM) é, portanto, uma condição séria e desafiadora com implicações importantes na Odontologia. O objetivo foi realizar uma revisão narrativa de literatura sobre as drogas antirreabsortivas e suas respectivas repercussões nos ossos maxilares. A revisão foi realizada através de busca bibliográfica utilizando descritores Decs/Mesh de interesse, em português e inglês, nas bases de dados PubMed, Biblioteca Virtual de Saúde (BVS) e Scielo. Após aplicação dos critérios de inclusão e exclusão, um total de 33 trabalhos foram selecionados para análise. Pode-se constatar que a terapia com agentes antirreabsortivos é complexa, sobretudo na prática odontológica, visto que a OMAM é uma complicação de difícil manejo. Em relação às condutas terapêuticas para esta condição, divide-se em terapia conservadora, cirúrgica ou adjuvante, todavia, não existem protocolos validados na literatura, bem como não há consistência quanto à indicação do intervalo de suspensão da administração da droga - "Drug Holiday". Desse modo, é importante que a equipe multidisciplinar busque estratégias que minimizem as complicações e promovam o controle no uso dessas drogas. Além disso, nota-se a necessidade de realizar investigações que contribuam com diretrizes para o manejo e controle dos efeitos adversos decorrentes da terapia com medicamentos antirreabsortivos. (AU)

Fibrous dysplasia. Clinical review and therapeutic management. / Displasia fibrosa. Revisión clínica y abordaje terapéutico.

Fibrous dysplasia is a skeletal disorder that is associated with a wide spectrum of clinical manifestations, including localized asymptomatic forms and extensive severe forms with severe bone deformities and endocrinological alterations, depending on age, location, extent and associated processes. Although the treatment of choice is based on bisphosphonates, the therapeutic efficacy of these agents in the control of disease activity remains uncertain. This article reviews the current data available on the treatment of this disease as well as the preliminary data on new therapeutic approaches.

Tratamiento conservador de osteonecrosis maxilar asociada a medicamentos refractaria mediante el uso de protocolo PENTO: reporte de un caso / Tratamento conservador da osteonecrose maxilar associada a medicamentos refratários usando o protocolo PENTO: relato de um caso / Conservative treatment of refractory medication-related osteonecrosis of the jaw using the PENTO protocol: A case report

Resumen Paciente de 78 años consulta por sangrado sin resolución, a nivel del reborde alveolar maxilar izquierdo. Con antecedentes de metástasis óseas tratadas con ácido zoledrónico endovenoso discontinuado por alta médica y tratamiento quirúrgico previo de osteonecrosis maxilar en sitio afectado. Se observó disrupción de continuidad con inflamación a nivel del reborde óseo, con salida de contenido hemático, purulento y necrótico. Radiográficamente se observó radiolucidez difusa y osteolítica del área afectada y tejido necrótico a nivel microscópico. Se realizó aseo del área afectada, enjuagues de clorhexidina 0,12%, administración de amoxicilina/acido clavulánico y de pentoxifilina 400 mg cada 12 horas y tocoferol 1000 UI cada 24 horas. Se evaluó al mes, donde se discontinua antibioterapia y se mantiene régimen establecido con controles cada 2 semanas. A los 6 meses se evidencia resolución completa, con cicatrización de la mucosa y del tejido óseo sin recidiva.

Resumo Paciente de 78 anos consultado por sangramento sem resolução, ao nível do rebordo alveolar superior esquerdo. Com história de metástases ósseas tratadas com ácido zoledrônico endovenoso descontinuado por alta médica e tratamento cirúrgico prévio de osteonecrose maxilar no local afetado. Foi observada interrupção da continuidade com inflamação ao nível da crista óssea, com extravasamento de sangue, conteúdo purulento e necrótico. Radiograficamente, radioluscência difusa e osteolítica da área afetada e tecido necrótico foram observadas ao nível microscópico. A área afetada foi limpa, enxágue com clorexidina 0,12%, amoxicilina / ácido clavulânico e 400 mg de pentoxifilina a cada 12 horas e 1000 UI de tocoferol a cada 24 horas. Foi avaliado em um mês, quando a antibioticoterapia é descontinuada e um regime estabelecido é mantido com controles a cada 2 semanas. Aos 6 meses, é evidenciada resolução completa, com cicatrização da mucosa e do tecido ósseo sem recorrência.

Abstract A 78-year-old patient seeks care for unresolved bleeding on the left maxillary alveolar ridge. He had a history of bone metastasis treated with IV zoledronic acid, which was discontinued after medical discharge and previous surgical treatment of osteonecrosis of the jaws in the affected site. Continuity disruption with inflammation at the bone ridge was observed, with blood, purulent, and necrotic exudate. The radiograph showed diffuse and osteolytic radiolucency of the affected area, and necrotic tissue was detected at a microscopic level. The affected area was rinsed with 0.12% chlorhexidine, 400 mg amoxicillin/clavulanic acid and pentoxifylline was administered every 12 hours, and tocopherol 1000 IU every 24 hours. The area was evaluated after a month. Antibiotic therapy was discontinued, and the patient continued to be monitored every two weeks. At six months, there is complete resolution, and mucosal and bone tissue healed without recurrence.

Effect of Zoledronic Acid and Alendronate on Bone Edema and Pain in Spontaneous Osteonecrosis of the Knee: A New Paradigm in the Medical Management / Efeito do ácido zoledrônico e do alendronato no edema ósseo e dor na osteonecrose espontânea do joelho: Um novo paradigma no manejo

Abstract Objective The aim of the present study was to determine the effect of combined zoledronic acid and alendronate therapy on bone edema and knee pain in cases of spontaneous osteonecrosis of the knee. We report our experience with this treatment. Methods A retrospective case series of 11 patients with spontaneous osteonecrosis of the knee confirmed by magnetic resonance image (MRI). The patients were treated with a single dose of 5 mg of intravenous zoledronic acid combined with 35 mg twice a week of oral alendronate, for 16 weeks. The visual analogue scale scores were noted before the beginning of the therapy, at 8 weeks, and at 16 weeks of follow-up. The size of the bone marrow edema adjacent to the lesion was measured on T2-weighted MRI coronal images at the beginning of the therapy and at 16 weeks. Results The average visual analogue scale score at 0 weeks was of 7.72, and of 0.81 at 16 weeks of therapy; the difference was statistically significant (p= 0.03). The mean bone marrow involvement at 0 weeks was of 80%, which reduced to 11.81% at 16 weeks of therapy. This change was statistically significant (p= 0.03). Conclusion Our data shows that the combination therapy causes early pain relief and reduction of the bone edema, and it is safe, effective and well-tolerated for a painful disease entity like spontaneous osteonecrosis of the knee.

Resumo Objetivo Determinar o efeito do tratamento combinado de ácido zoledrônico e alendronato no edema ósseo e na dor no joelho em casos de osteonecrose espontânea do joelho. A experiência dos autores com este tratamento é relatada. Métodos Série de casos retrospectiva, incluindo 11 pacientes com osteonecrose espontânea do joelho confirmada por ressonância magnética. Os pacientes foram tratados com uma dose intravenosa única de 5 mg de ácido zoledrônico combinada com 35 mg de alendronato oral, 2 vezes por semana, por 16 semanas. Os escores da escala visual analógica foram aferidos antes do começo do tratamento, em 8 semanas e em 16 semanas de acompanhamento. O tamanho do edema da medula óssea adjacente à lesão foi medido em imagens de ressonância magnética coronal ponderadas em T2 no início do tratamento e em 16 semanas. Resultados O escore médio da escala visual analógica em 0 semanas foi de 7,72, contra 0,81 em 16 semanas de tratamento, uma diferença estatisticamente significativa (p= 0,03). O envolvimento médio da medula óssea em 0 semanas foi de 80%, e foi reduzido para 11,81% em 16 semanas de tratamento, uma diferença também estatisticamente significativa (p= 0,03). Conclusão Os dados mostram que a terapia combinada proporciona alívio da dor inicial e redução do edema ósseo, sendo segura, eficaz e bem tolerada em uma enfermidade dolorosa como a osteonecrose espontânea do joelho.