Free buccal fat pad graft for the bone defect filling of medication-related osteonecrosis of the jaws: A novel surgical approach.

Surgical intervention for medication-related jaw osteonecrosis (MRONJ) is currently the main treatment method, offering a higher healing rate than conservative approaches. However, the management of bony defects after sequestrectomy remains a challenging issue due to poor vascularization from the drug effect. The use of pedicled buccal fat pad (PBFP) for filling bone defects has become common and effective but is limited to the posterior maxillary region. To add to the advantages of the buccal fat pad, we explored a novel treatment approach using a free buccal fat pad (FBFP) to fill bone defects other than the posterior maxilla. While the FBFP has been employed in oral defect reconstruction, currently published cases have been utilized in recipient sites with good blood supply. There has yet to be any usage in poor vascularization defects like MRONJ. This article describes that the FBFP was used to fill the surgical defects of 8 patients who were diagnosed with MRONJ and who underwent sequestrectomy and saucerization. During follow-up visits, there was excellent wound healing and no significant tissue depression. Based on successful treatment experiences, FBFP is a reliable therapeutic option for the management of poor vascularization defects like MRONJ treated through surgical intervention.

Effect of anti-resorptive therapy on implant failure: a systematic review and meta-analysis.

PURPOSE: This review was conducted to systematically assess the impact of bisphosphonates (BPs) and denosumab, used as anti-resorptive therapies, on the incidence of dental implant failure. METHODS: Electronic and manual searches were performed in accordance with the described search protocol. Only articles that met the inclusion criteria were selected. The primary outcome was implant failure, while secondary outcomes included biological complications and comorbidities. Following data extraction, a quality assessment and meta-analysis were conducted. RESULTS: Fourteen eligible studies were included in the analysis following a qualitative evaluation. BP administration, regardless of the timing of anti-resorptive therapy, did not significantly increase the risk of implant failure (odds ratio [OR], 1.40; 95% confidence interval, 0.83-2.34). Subgroup analysis revealed a slightly higher, although statistically insignificant, risk of failure in patients with a follow-up period of 3 years or more compared to those with a follow-up duration of less than 3 years (with ORs of 2.82 and 1.53, respectively). Due to a lack of eligible studies, a meta-analysis for denosumab could not be conducted. CONCLUSIONS: Our findings suggest that BP treatment does not compromise the survival of dental implants. Specifically, in patients with osteoporosis, implant failure rates were not significantly influenced by the administration of BPs before the placement of dental implants, suggesting that low-dose BP therapy may not contraindicate implant placement. Nevertheless, regular check-ups and maintenance periodontal treatment must not be neglected, and concomitant biological factors should be considered to ensure the long-term success of implant rehabilitation.

The effectiveness of autologous platelet concentrates in prevention and treatment of medication-related osteonecrosis of the jaws: A systematic review.

The systematic review aims to answer the PICOS question: "Are the autologous platelet concentrates (APCs) an effective strategy in prevention and/or treatment of patients at risk of/affected by medication-related osteonecrosis of the jaws (MRONJ)?". A literature search was conducted via PubMed, MEDLINE, EMBASE, and CINAHL (January 2006 - September 2023). 30 articles were included, evaluating preventive (n = 8*) and treatment strategies (n = 23*). The risk of bias and quality of studies were assessed utilising ROB-2, ROBIN-1 and GRADE criteria. Meta-analysis was undertaken for eligible studies. The application of APCs demonstrated a statistically significant effectiveness in prevention of MRONJ in 86.13% (p < 0.001) but failed to achieve the same level of certainty in treatment of established MRONJ in 83.4% (p = 0.08). High levels of bias were identified; thus, the results should be interpreted with caution. More high quality prospective randomised controlled trials are needed to further evaluate the effectiveness of APCs in management of MRONJ.

Recognizing bisphosphonate-induced ear osteonecrosis in primary care: a case report.

INTRODUCTION: Medication-related ear canal osteonecrosis (MRECO) is a growing concern linked to prolonged anti-resorptive medication use. Despite primary care providers being key prescribers of these medications, there is limited information about MRECO in primary care literature. This article presents a case of bisphosphonate-induced osteonecrosis of the external auditory canal (EAC), emphasizing the vital role of primary care providers in identifying this rare yet significant side effect of anti-resorptive medication. MAIN SYMPTOMS AND CLINICAL FINDINGS: A 65-year-old female, on long-term alendronic acid for osteoporosis, presented to primary care with a 2-year history of left-sided ear blockage and itchiness. Despite prolonged topical treatment for ear wax, symptoms persisted, leading to an Otolaryngology referral. Microsuction revealed exposed bone in the left EAC. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: A computed tomography scan confirmed bony erosion of the left EAC, and in the absence of other osteonecrosis risk factors, bisphosphonate-induced osteonecrosis was diagnosed. Management involved bisphosphonate discontinuation, regular aural toilet, and topical treatment, achieving complete ear canal epithelialisation within 6 months. CONCLUSION: MRECO, a rare complication of anti-resorptive therapy, is anticipated to rise with increasing antiresorptive medication use in the ageing population. Unexplained ear symptoms in those with a history of current or prior anti-resorptive therapy should raise clinical concern, prompting evaluation for exposed bone in the EAC. Raising awareness of MRECO among primary care providers is crucial for early diagnosis and timely management.

Surgical and conservative treatment outcomes of medication-related osteonecrosis of the jaw located at tori: a retrospective study.

PURPOSE: Tori and exostoses are considered risk factors for the development of medication-related osteonecrosis of the jaw (MRONJ). The aims of this study were to present the prevalence of MRONJ located at tori in the Copenhagen ONJ Cohort, evaluate the surgical treatment of MRONJ located at tori and explore trauma to tori as an additional risk factor in patients on antiresorptive medication. METHODS: Data from a consecutive series of 506 patients with MRONJ (Copenhagen ONJ Cohort) were reviewed for the presence of tori and MRONJ located at tori. Demographic and medical data were analyzed, and healing outcomes and pain after the prophylactic removal of tori, surgical treatment of MRONJ located at tori, and conservative treatment of MRONJ located at tori were evaluated and compared using Fisher's exact test. RESULTS: MRONJ located at tori was frequent and could be identified in 53% of the patients with tori, which accounts for a prevalence of 5.1% in the entire cohort. Of the 28 surgically treated patients, 27 (96.4%) healed uneventfully with no exposed bone after their first or second revision surgery. Fourteen (41.2%) patients with tori underwent therapeutic removal, eight (23.5%) underwent prophylactic removal, and six (17.6%) underwent both therapeutic and prophylactic removals. Two (33.3%) of the six conservatively treated patients healed spontaneously. Both treatment types resulted in a significant decrease in pain. CONCLUSION: Prophylactic and therapeutic surgical removal of tori are reliable treatments and should be considered if a patient's general health allows surgery. TRIAL REGISTRATION: The study was approved by the Regional Scientific Ethical Committee (H-6-2013-010) on November 20, 2013, and was retrospectively registered.

Italian position paper (SIPMO-SICMF) on medication-related osteonecrosis of the jaw (MRONJ).

OBJECTIVE: This paper aims to describe the 2023 update position paper on MRONJ developed by the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Maxillofacial Surgery (SICMF). METHODS: This is the second update following the 2013 and 2020 Italian position papers by the Expert panel, which is a representation of the two scientific societies (SIPMO and SICMF). The paper is based on an extensive analysis of the available literature from January 2003 to February 2020, and the subsequent review of literature conducted between March 2020 and December 2022 to include all new relevant published papers to confirm or modify the previous set of recommendations. RESULTS: This position paper highlights the main issues of MRONJ on risk estimates, disease definition, diagnostic pathway, individual risk assessment, and the fundamental role of imaging in the diagnosis, classification, and management of MRONJ. CONCLUSION: The Expert Panel confirmed the MRONJ definition, the diagnostic work-up, the clinical-radiological staging system and the prophylactic drug holiday, as recognized by SIPMO-SICMF; while, it presented novel indications regarding the categories at risk of MRONJ, the prevention strategies, and the treatment strategies associated with the therapeutic drug holiday.

[Osteoporotic vertebral fractures of the thoracic and lumbar spine]. / Osteoporotische Wirbelkörperfrakturen der Brust- und Lendenwirbelsäule.

The frequency of osteoporotic vertebral fractures in the clinical routine is increasing due to the demographic change. They are the most frequent fractures associated with osteoporosis and affect an especially morbid and vulnerable group of patients. These fractures often occur after minor trauma or spontaneously. Pain is the predominant symptom, whereas mechanical stability is mostly sufficient, in comparison to vertebral fractures after high-energy trauma, and is not a predominant indication for surgery. These fractures can be described using the classification for fractures associated with osteoporosis and the corresponding treatment recommendations are guided by them. Besides the specific treatment of osteoporotic vertebral fractures, a holistic treatment of patients taking pre-existing comorbidities into consideration is decisive. A mobilization as quickly as possible and treatment of the underlying osteoporosis are important to prevent further fractures.

Navigating the complexities and controversies of medication-related osteonecrosis of the jaw (MRONJ): a critical update and consensus statement.

OBJECTIVES: To provide a critical update identifying the knowledge gaps and controversies in medication-related osteonecrosis of the jaw (MRONJ) within the Belgian healthcare context and outline opportunities for improvement and research in these areas. METHODS: A literature review was performed to identify guidelines from international clinical societies in oncology or oral and maxillofacial surgery on diagnosing, preventing, and treating MRONJ. The recommendations were critically assessed in light of recent developments in the field and confronted with the clinical experience of experts. RESULTS: Despite progress in the diagnostic criteria of MRONJ, the continued need for an 8-week timeout period should be reconsidered. Furthermore, 3D imaging techniques should be introduced to improve diagnosis and staging. The staging system remains ambiguous regarding Stage 0 MRONJ, and ongoing confusion exists regarding the term non-exposed MRONJ. The prevention of MRONJ should be tailored, considering the individual patient's risk of MRONJ, frailty, and life expectancy. More research seems needed into the efficacy and safety of drug holidays, considering the risks of rebound remodeling on fractures. With renewed interest in surgical and adjunct management techniques, adequately designed clinical studies are needed to help translate trial outcomes into universally applicable treatment guidelines taking into account individual patient characteristics. CONCLUSIONS: Important knowledge gaps remain and hamper the development of clinical guidelines. Several controversies were identified where consensus is lacking, and further harmonization between stakeholders is necessary. Finally, the need for randomized controlled comparative clinical trials in MRONJ resonates harder than ever to identify the best treatment for individual patients.

Bone-modifying agents for non-small-cell lung cancer patients with bone metastases during the era of immune checkpoint inhibitors: A narrative review.

During the course of lung cancer progression, bone metastases occur in about 40% of patients. Common complications associated with bone metastases in lung cancer patients include musculoskeletal pain, pathologic fractures, spinal cord compression, and hypercalcemia. We discuss the efficacy of bone-modifying agents (BMAs) in reducing skeletal-related events (SREs) and improving cancer-related outcomes, particularly in patients with stage IV non-small-cell lung cancer with bone metastases. In addition, the combined effects of BMAs with radiotherapy or immunotherapy in reducing SREs in patients with lung cancer and bone metastases are explored.

Dentists' Awareness of Medication-Related Osteonecrosis of the Jaw (Risk Factors, Drugs, and Prevention) in the Republic of Croatia.

Introduction: Antiresorptive drugs (AR) have been used for many years in the treatment of various bone conditions such as osteoporosis, osteopenia, Paget's disease, bone metastases, multiple myeloma and the associated malignant hypercalcemia. As a side effect of AR therapy, medication-related osteonecrosis of the jaw, which affects the mandible more commonly than the maxilla, (MRONJ) has become an increased risk regarding patients' health and quality of life. The incidence of osteonecrosis has increased significantly in the last few years. One of the main methods of the disease prevention is the education of patients and doctors of dental medicine (DDMs). This is evidenced by the national program of information and prevention of antiresorptive therapy side effects, which was also the impetus for this study. Purpose: This study aims to test the knowledge of DDMSs on AR, especially on bisphosphonate (BF) therapy, MRONJ as well as on the risk factors of the disease itself. Material and methods: 458 DDMs from the Republic of Croatia participated in the survey and responded by an anonymous questionnaire to questions about the knowledge of AR/BF and the risk of MRONJ. Results: The results showed that 36.68% of DDMs do not know that MRONJ is the main complication of AR/BF therapy. The results are significantly different in terms of academic degree, specialization, workplace, and work experience. 60.26% of respondents do not know the main indications for AR/BF use, 53.26% do not know the factors affecting the onset of the disease, and 42.58% do not know which therapy is not recommended for patients on AR/BF therapy. 93.89% of respondents expressed the desire to educate on this issue. This current study was carried out to further investigate the pilot study findings which was conducted in the year 2015, but it had a significantly lower number of participants. Conclusion: This research suggests that further education of DDMS on this topic is necessary to prevent or to start early treatment of MRONJ.

Treatment rates and healthcare costs of patients with fragility fracture by site of care: a real-world data analysis.

In a characterization of treatment rates and healthcare costs among patients with an osteoporotic-related fragility fracture overall and by site of care, costs were high and treatment rates were low. PURPOSE: Osteoporotic fractures can be debilitating, even fatal, among older adults. The cost of osteoporosis and related fractures is projected to increase to more than $25 billion by 2025. The objective of this analysis is to characterize disease-related treatment rates and healthcare costs of patients with an osteoporotic fragility fracture overall and by site of fracture diagnosis. METHODS: In this retrospective analysis, individuals with fragility fractures were identified in the Merative MarketScan® Commercial and Medicare Databases among women 50 years of age or older and diagnosed with fragility fracture between 1/1/2013 and 6/30/2018 (earliest fracture diagnosis = index). Cohorts were categorized by clinical site of care where the diagnosis of fragility fracture was made and were continuously followed for 12 months prior to and following index. Sites of care were inpatient admission, outpatient office, outpatient hospital, emergency room hospital, and urgent care. RESULTS: Of the 108,965 eligible patients with fragility fracture (mean age 68.8), most were diagnosed during an inpatient admission or outpatient office visit (42.7%, 31.9%). The mean annual healthcare costs among patients with fragility fracture were $44,311 (± $67,427) and were highest for those diagnosed in an inpatient setting ($71,561 ± $84,072). Compared with other sites of care at fracture diagnosis, patients diagnosed during an inpatient admission also had highest proportion of subsequent fractures (33.2%), osteoporosis diagnosis (27.7%), and osteoporosis therapy (17.2%) during follow-up. CONCLUSION: The site of care for diagnosis of fragility fracture affects treatment rates and healthcare costs. Further studies are needed to determine how attitude or knowledge about osteoporosis treatment or healthcare experiences differ at various clinical sites of care in the medical management of osteoporosis.

Eficácia e segurança de romosozumabe para o tratamento de osteoporose grave em mulheres na pós-menopausa: revisão sistemática e meta-análise em rede / Efficacy and safety of romosozumab for the treatment of severe osteoporosis in postmenopausal women: systematic and network meta-analysis

Introdução: A osteoporose é uma das principais causas de morbimortalidade, principalmente em idosos e mulheres na pós-menopausa, devido ao aumento da fragilidade óssea e maior suscetibilidade a fraturas. Objetivo: Avaliar a eficácia e segurança do romosozumabe, comparado aos tratamentos farmacológicos atualmente disponíveis no Sistema Único de Saúde para o manejo de mulheres na pós-menopausa com osteoporose grave e alto risco de fraturas. Métodos: Foi realizada uma busca seguida por meta-análises indiretas, por ensaios clínicos randomizados (ECR) nas bases PubMed Central e Medline, Embase e Cochrane Library e por busca manual. O risco de viés (RoB 2.0) e a qualidade da evidência (GRADE) foram analisados. Meta-análises indiretas foram realizadas para desfechos de fraturas, densidade mineral óssea e eventos adversos. Resultados: Sete ECR (n= 19.951 mulheres) foram incluídos nesta revisão. Romosozumabe seguido de alendronato reduziu risco de fraturas não vertebrais em 12 meses (RR: 0,64, IC 95%: 0,49-0,84; alta certeza de evidência) e em 24 meses (RR: 0,52, IC 95%: 0,43-0,64; (alta certeza de evidência) na comparação ao alendronato. Achados semelhantes foram identificados para outros desfechos. Ácido zoledrônico foi associada a maior risco de descontinuação por evento adverso que placebo (RR: 1,02, IC 95%: 1,01-1,03). Conclusão: Foi identificado que romosozumabe ou romosozumabe seguido por alendronato são eficazes e seguros na comparação com alendronato.

Background: Osteoporosis is a major cause of morbidity and mortality, especially in the elderly and postmenopausal women, due to increased bone fragility and greater susceptibility to fractures. Objective: To evaluate the efficacy and safety of romosozumab, compared to pharmacological treatments currently available in the Unified Health System of Brazil for the management of postmenopausal women with severe osteoporosis and high risk of fractures. Methods: A search was carried out followed by indirect meta-analyses, randomized controlled trials (RCTs) in PubMed Central and Medline, EMBASE, and Cochrane Library databases and manual search. Risk of bias (RoB 2.0) and quality of evidence (GRADE) were assessed. Indirect frequentist meta-analyses were carried out for outcomes related to fractures, bone mineral density, and adverse events. Results: Seven RCTs (n= 19,951 woman) were included in this review. Romosozumab followed by alendronate reduced the risk of non-vertebral fractures at 12 months (RR: 0.64, 95% CI: 0.49-0.84; high certainty of evidence) and at 24 months (RR: 0.52, CI 95 %: 0.43-0.64; (high certainty of evidence) in comparison to alendronate. Similar findings were identified for other outcomes. Zoledronic acid was associated with a higher risk of discontinuation due to adverse events than placebo (RR: 1.02, 95% CI: 1.01-1.03). Conclusion: This review identified that romosozumab or romosozumab followed by alendronate are effective and safe compared to alendronate.

Avaliação da resposta óssea de uma superfície de implante revestida com odanacatib em ratas ovariectomizadas: estudo experimental in vivo / Evaluation of the bone response of an odanacatib coated implant surface in ovariectomized rats: in vivo experimental study

Atualmente novos princípios ativos de função reabsortiva têm ganhado campo de estudo para avaliar seus mecanismos e comportamento biológico. Com isso, um novo antirreabsortivo, inibidor da catepsina K tem apresentado efeito positivo na osseointegração. Este estudo tem como objetivo avaliar a resposta óssea da superfície de implantes revestida por duplo ataque ácido e Odanacatib (MK-0822) em ratas ovariectomizadas. Neste estudo foram utilizadas ratas (Albinus, Wistar) ovariectomizadas ou sham (placebo). Cinquenta e dois (52) tiveram as superfícies revestidas por duplo ataque ácido e MK-0822 a 0,06 mg/ml através do método biomimético, e 48 implantes foram instalados em tíbias de ratas ovariectomizadas ou sham. Microscopia eletrônica de varredura (MEV) e energia dispersiva de raios-x (EDS) foram realizadas em 4 implantes após tratamento de superfície, para análise da topografia e composição química, além da realização da análise do ângulo de contato em 16 discos de titânio comercialmente puro tratados com as mesmas superfícies. Aos 15 e 40 dias após instalação de implantes (n=6), foi realizada microtomografia computadorizada. Dados quantitativos foram avaliados adotando-se o nível de significância p< 0,05. Além dos resultados topográficos favoráveis para os grupos tratados com MK-0822, os resultados microtomográficos apresentaram diferença estatisticamente significante entre os grupos SHAM e OVX na maioria dos parâmetros (p< 0,05). Ainda assim, os grupos tratados com MK-0822 apresentaram resultado semelhante ou maior, porém sem diferença estatística, em relação ao grupo controle em todos os parâmetros (TV, BV, BV ̸TV, Tb.Sp e Tb.N)(AU)

Currently new active principles of resorptive function have gained field of study to evaluate their mechanisms and biological behavior. Thereby a new anti-absorbent, cathepsin K inhibitor has had a positive effect on osseointegration. This study aims to evaluate the bone response of the surface of implants coated by double acid-etched and Odanacatib (MK-0822) in ovariectomized rats. In this study, either ovariectomized rats (Albinus, Wistar) or sham (placebo) have been used. Fifty-two (52) implants had the surfaces coated with double acid-etched and MK-0822 at 0,06 mg/ml by the biomimetic method and 48 implants were installed on sham or ovariectomized rat tibias. Scanning electron microscopy (SEM) and X-ray dispersive energy (EDS) were performed in 4 implants after surface treatment for analysis of topography and chemical composition, in addition to performing contact angle analysis on 16 commercially pure titanium discs treated with the same surfaces. At 15 and 40 days after implant installation, microcomputer tomography was performed. Quantitative data was evaluated by adopting the significance level of p< 0.05. Besides the favorable topographic results to MK-0822 coated implants group, the microtomographic results presents statistically significant differences between the SHAM and OVX groups at most of the parameters (p< 0,05). Nevertheless, the MK-0822 coated group presents similar or higher values, although without statistic differences related to the control group in all parameters (TV, BV, BV ̸TV, Tb.Sp and Tb.N)(AU)

Analysis of the Degree of Information of Dental Surgeons about Antiresorptive Drugs According to the Time Since Graduation in Dentistry

ABSTRACT Objective: To determine the level of scientific information of dental surgeons who carry out their professional activities in Brazil about antiresorptive drugs and indicated pharmacological procedures aiming at the prevention of osteonecrosis of the jaws and the therapy of drug sequelae that may occur, considering the time since graduation in Dentistry. Material and Methods: This is a quantitative cross-sectional study in which 339 dentists were consulted using the virtual questionnaire containing topics of personal nature, elements contained in the anamnesis carried out and knowledge about antiresorptive drugs, including indications, adverse effects and treatments applied. Chi-square and Fisher's exact tests were performed to analyze associations of data described by absolute and relative frequencies with professionals' time since graduation. All analyses were performed using the R software, with a 5% significance level. Results: Those who revealed to have graduated for more than five years with the highest academic degree were those who demonstrated maximum knowledge of antiresorptive drugs or revealed that, somehow, they had information about them (p<0.05). Conclusion: Dental surgeons in Brazil who have more than five years since graduation have more scientific information about antiresorptive drugs and pharmacological procedures, which can positively contribute to the prevention of osteonecrosis of the jaws and treatment of drug sequelae that may occur.

[Therapeutic alternatives for drug-associated maxillary osteonecrosis (MRONJ): reports of two clinical cases and review of the literature]. / Alternativas terapéuticas de osteonecrosis maxilar asociada a medicamentos (ONMAM): reportes de dos casos clínicos y revisión de la literatura.

Introduction: Drug-associated Maxillary Osteonecrosis is one of the most relevant adverse effects in treatment with antiresorptive drugs such as bisphosphonates and denosumab. Oncological conditions such as multiple myeloma, breast cancer, prostate, and bone-metabolic disorders such as osteoporosis lead the indications for these antiresorptive therapies. Treatment is complex because the disease is often refractory. Pharmacological, conservative and surgical treatments are described. Objective: The aim of this study is to report two clinical cases of MRONJ treated with two different therapeutic protocols and the analysis of the available literature on these aspects based on the clinical classification defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS). Conclusion: Patients who develop clinical signs of great morbidity associated with MRONJ, may see their quality of life conditioned and suffer a worsening of their underlying pathology. MRONJ treatment is conditioned by the stage of the disease, its success depends on interdisciplinary management and strict medical and dental clinical follow-up, as well as rigorous monitoring to prevent or detect future recurrences early.

Introducción: La Osteonecrosis Maxilar asociada a Medicamentos (ONMAM) constituye uno de los efectos adversos más relevantes en el tratamiento con drogas antirresortivas como bifosfonatos y denosumab. Patologías oncológicas como mieloma múltiple, cáncer de mama, próstata, y alteraciones óseas-metabólicas como la osteoporosis lideran las indicaciones para estas terapias antirresortivas. El tratamiento es complejo debido a que muchas veces, la enfermedad es refractaria a la terapéutica aplicada. Se describen tratamientos farmacológicos, conservadores y quirúrgicos. Objetivo: El objetivo de este trabajo es reportar dos casos clínicos de ONMAM tratados con dos protocolos terapéuticos diferentes y el análisis de la literatura disponible en la actualidad sobre estos aspectos en base a la clasificación clínica definida por la American Association of Oral and Maxillofacial Surgeons (AAOMS). Conclusión: Los pacientes que desarrollan cuadros clínicos bucales de gran morbilidad como lo es ONMAM, pueden ver condicionada su calidad de vida y sufrir un agravamiento de su patología de base. El tratamiento de ONMAM está condicionado al estadio de la enfermedad, el éxito del mismo depende del manejo interdisciplinario y de un estricto seguimiento clínico médico y odontológico, así como también un riguroso monitoreo para evitar o detectar precozmente futuras recurrencias.

A systematic review assessing occurrence of medication-related osteonecrosis of the jaw following dental procedures

Aim: This study aimed to systematically review existing literature regarding the association between dental procedures­such as tooth extractions and periodontal therapy­and occurrence of medication-related osteonecrosis of the jaw (MRONJ) in individuals using bone-modifying drugs. Methods: Search strategies were performed in PubMed, Scopus, Web of Science and Cochrane Library for a timeframe ending in December 2021. Study selection, data extraction and risk of bias were analyzed independently by two researchers. Three meta-analyses were performed, estimating the crude risk ratio (RR), the adjusted odds ratio (OR) and the adjusted hazard ratio (HR) for the association between tooth extraction and MRONJ. Results: Of the 1,654 studies initially retrieved, 17 were ultimately included. The majority of patients with MRONJ in these studies were female, with a mean age of 64 years. Zoledronic acid was the most commonly used drug among patients with MRONJ, and cancer was the most frequent underlying health condition. Regarding the performed meta-analyses, crude and adjusted analyses demonstrated that tooth extraction increased the risk for MRONJ by 4.28 (95% confidence interval [95%CI]: 1.73­10.58), the OR for MRONJ by 26.94 (95%CI: 4.17­174.17), and the HR for MRONJ by 9.96 (95%CI: 4.04­24.55). Conclusion: It was concluded that performing dental procedures, especially tooth extraction, in patients using bone-modifying drugs increased the risk of MRONJ occurrence and, therefore, should be avoided. Further studies, using adjusted data, are warranted

Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial.

Background: Giant-cell tumor of bone (GCTB) is a relatively benign, but locally aggressive osteoclastogenic stromal tumour of the bone. Although denosumab has been approved as an monoclonal antibody against RANK ligand for the treatment of GCTB, few clinical trials of the benefit in tumor response have been conducted to prove the efficiency in Chinese population. Objectives: In this multicentric, random controlled, clinical trial, 160 patients were enrolled to compare the therapeutic efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable GCTB. Methods: Between 2nd Jan 2015 and 1st Jan 2018, 160 adults (aged ≥ 18 years) with ①surgically unsalvageable GCTB, ②surgically salvageable GCTB with planned surgery expected to result in severe morbidity were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg once every 4 weeks with loading doses of 120 mg subcutaneously admininstered on days 8 and 15; n = 80) or intravenous zoledronic acid (ZA group; 4 mg once every 4 weeks; n = 80) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals. Results: Denosumab and zoledronic acid had similar tumor responses (p = 0.118) and clinical benefits (p = 0.574). Disease progression was observed in fewer patients in the DB group (12.5%) than ZA group (15.0%). Denosumab caused fatigue (p = 0.001) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.059) and hypotension (p = 0.059). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was the same for the ZA group and the DB group (p = 0.425). The accumulate recurrence-free survival rate at 4-year follow-up is higher in DB group (p = 0.035). Conclusions: Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable GCTB.

Dental Evaluation Prior to Cancer Therapy.

A comprehensive oral examination and dental care prior to the start of cancer therapy is the standard of care in many cancer centers. This is because good oral health will likely minimize the undesirable complications such as opportunistic infections during cancer therapy. As the considerations differ between anti-neoplastic regimens, this chapter discusses the indications and rationale when planning and executing a treatment plan for patients undergoing various cancer therapies.

Corrigendum: When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis.

[This corrects the article DOI: 10.3389/fendo.2021.782118.].

Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons.

Antiresorptives are the most widely prescribed drugs for the treatment of osteoporosis. They are also used in malignant bone metastases, multiple myeloma, and Paget's disease, and provide therapeutic efficacy on those diseases. However, it was reported that the occurrence of osteonecrosis of the jaw (ONJ) could be related to antiresorptive exposures, and there have been many cases regarding this issue. Therefore, a clearer definition and treatment guidelines were needed for this disease. The American Society for Bone and Mineral Research and the Amnerican Association of Oral and Maxillofacial Surgeons reported statements on bisphosphonate-related ONJ (BRONJ), and a revised version was recently presented. In the revised edition, the diagnosis BRONJ was changed to medication-related ONJ (MRONJ), which reflects consideration of the fact that ONJ also occurs for denosumab, a bone resorption inhibitor of the receptor activator of the nuclear factor-κB ligand antibody family, and bevacizumab, an anti-angiogenesis inhibitor. The Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons had collectively formed a task force for the preparation of an official statement on MRONJ based on a previous position paper in 2015. The task force reviewed current knowledge and coordinated dental and medical opinions to propose the guideline customized for the local Korean situation.