Bisphosphonate-associated osteonecrosis of the jaw

双膦酸盐相关的颌骨坏死
  • 文章类型: Journal Article
    药物相关的颌骨坏死(MRONJ)是一种药物不良反应,会影响接受BMA和AA治疗的患者的下颌骨和上颌骨,导致骨骼的进行性破坏和死亡。迄今为止,口腔健康预防措施仍然是减少MRONJ发病率的最有效策略,and,在这个意义上,主要目标是诊断,请客,根除任何可能危害口腔健康的口腔疾病。本系统综述旨在调查假设BMA的患者对MRONJ的认识。
    进行了系统的文献检索,选择关注患者对MRONJ风险认识的研究。
    本综述包括6项研究。总的来说,对483例患者进行了评估。在483名患者中,391人不知道MRONJ发作的可能性(391/483,81%),92人知道(92/483,19%)。
    患者对MRONJ风险缺乏认识的问题呈现出不同的复杂性(“什么?”,“谁?”“哪里?”,“什么时候?”和“为什么?”)。在其因果因素中,与患者的沟通水平不足,医疗保健专业人员之间缺乏合作,这与责任和义务义务的个人主义观点有关。MRONJ是一种药物不良反应,如果不及时诊断和治疗,会极大地影响患者的生活质量。因此,患者必须充分意识到不良风险和预防措施的重要性,这意味着多学科团队的每个成员进行有效和详尽的沟通。应促进有效的团队合作和协作护理,以积极影响患者的意识。
    UNASSIGNED: Medication-related osteonecrosis of the Jaw (MRONJ) is an adverse drug reaction that affects the mandible and maxilla of patients exposed to BMA and AA therapies, causing the progressive destruction and death of bone. To date, oral health preventive measures remain the most effective strategy to reduce MRONJ incidence, and, in this sense, the major goal is to diagnose, treat, and eradicate any oral diseases that could compromise oral health. The present systematic review aims to investigate the awareness of MRONJ among patients assuming BMAs.
    UNASSIGNED: A systematic literature search was performed, selecting studies that concern the awareness of patients of the risk of MRONJ.
    UNASSIGNED: Six studies were included in this review. In total, 483 patients were evaluated. Of the 483 included patients, 391 were not aware of the possibility of MRONJ onset (391/483, 81%) and 92 were aware of it (92/483, 19%).
    UNASSIGNED: The problem of patient\'s lack of awareness with respect to MRONJ risk presents different layers of complexity (\"what?\", \"who?\", \"where?\", \"when?\" and \"why?\"). Among its causal factors, there are an inadequate level of communication with patients and the lack of collaboration between healthcare professionals, which is related to an individualistic view of liability and deontological duties. MRONJ is a drug adverse reaction that can greatly affect the quality of life of patients if not promptly diagnosed and treated. Therefore, patients must be fully aware of the risks of adverse and the importance of preventive measures, which imply effective and exhaustive communication by each member of the multidisciplinary team. Effective teamwork and collaborative care should be promoted to positively impact patients\' awareness.
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  • 文章类型: Journal Article
    药物相关的颌骨坏死(MRONJ)是一种罕见的,但是由双膦酸盐引起的毁灭性疾病,核因子κB受体激活剂配体抑制剂,抗血管生成药物,和改善疾病的抗风湿药。虽然MRONJ的临床范围很广,有一组患者使用抗生素和保守性手术清创不能改善,导致病理性骨折,引流瘘管,和/或骨髓炎。对于受影响严重的个人,唯一的治疗方法是手术切除与微血管游离皮瓣重建。MRONJ的病因尚不清楚,因为缺乏对与各种药物作用机制有关的疾病的生物学基础的了解。这种有限的知识导致通过临床表现而不是基础病理学对患者进行分类。因此,本文的目的是在已知诱导甲羟戊酸途径的药物的背景下,提出MRONJ通过甲羟戊酸途径的机制框架,并探索潜在的新疗法.
    Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but devastating condition caused by bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, anti-angiogenic medications, and disease-modifying antirheumatic drugs. While the clinical spectrum of MRONJ has a wide range, there is a subgroup of patients that do not improve with antibiotics and conservative surgical debridement resulting in pathologic fractures, draining fistulas, and/or osteomyelitis. For the severely affected individuals, the only cure is surgical resection with micro-vascular free flap reconstruction. The etiology of MRONJ is unknown because of the lack of understanding of the biological underpinnings of the disorder connected to the mechanisms of action of the various medications. This limited knowledge has resulted in the classification of patients by clinical presentation rather than underlying pathology. Therefore, the aim of this article is to present a mechanistic framework of MRONJ through the mevalonate pathway in the context of the medications that are known to induce it and explore potential novel therapeutics.
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  • 文章类型: Journal Article
    目的:绘制当前关于在双膦酸盐(BF)治疗下拔牙后药物相关的颌骨坏死(MRONJ)的关联/因果关系的科学图景,以确定知识差距并指导未来的研究。
    方法:本综述使用PCC策略(P=患者;C=概念;C=背景)。
    方法:MEDLINE/PubMed,Scopus,WebofScience/ClarivateAnalytics,使用灰色文献数据库。
    方法:由两名独立评审员进行搜索,直至2024年4月。包括涉及先前在人或动物中使用BF和拔牙的研究。在176项研究中,73例(41.4%)在动物中,103人(58.5%)。巴西在动物研究方面处于领先地位(n=14;19.1%),而意大利在人体研究中处于领先地位(n=14;13.6%)。唑来膦酸是引用最多的BF(在动物中为79.4%;在人类中为34.9%),静脉给药最常见(动物为38.3%;人类为35.9%)。下颌骨是主要的提取部位(动物中n=36;人类中n=41)。在91.7%的动物研究中,观察到与骨坏死体征和症状相符的后遗症,以骨坏死最为常见(n=39;53.4%)。在人类中,93.2%的研究提出了239个后遗症,骨坏死(n=53;22.1%)被引用最多。后遗症的主要位置是下颌骨(动物中n=36;人类中n=41)。
    结论:动物研究强调骨暴露,特别是使用鼠类模型,巴西做出了重大贡献。在人类研究中,骨坏死是MRONJ的主要后遗症,意大利的研究人员已经报道了这一点。
    结论:这些发现强调了仔细考虑和监测有双膦酸盐使用史和正在进行拔牙的患者的重要性。强调MRONJ的潜在风险。
    To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research.
    This review used the PCC strategy (P = Patient; C = Concept; C = Context).
    The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used.
    Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4 %) were in animals, and 103 (58.5 %) were in humans. Brazil led in animal studies (n = 14; 19.1 %), while Italy led in human studies (n = 14; 13.6 %). Zoledronic acid was the most cited BF (79.4 % in animals; 34.9 % in humans), with intravenous administration being most frequent (38.3 % in animals; 35.9 % in humans). The mandible was the main extraction site (n = 36 in animals; n = 41 in humans). In 91.7 % of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n = 39; 53.4 %). In humans, 93.2 % of studies presented 239 sequelae, with bone necrosis (n = 53; 22.1 %) being the most cited. The main location of sequelae was the mandible (n = 36 in animals; n = 41 in humans).
    Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy.
    These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ.
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  • 文章类型: Journal Article
    设计了一项系统评价,以研究口服双膦酸盐(BP)治疗对绝经后妇女牙种植体骨整合和BP相关颌骨坏死(BRONJ)发生率的影响。多个电子数据库,包括MEDLINE(PubMed),EMBASE,和Scopus,搜索了自1990年以来发表的所有符合条件的文章。通过搜索信息源检索到的所有标题和摘要均由两名作者根据资格标准独立评估。病例数为11~235,对照数为14~343。阿仑膦酸盐用于所有其他研究。在六项研究中使用了利塞膦酸盐,而伊班膦酸钠在四项研究中使用。病例中的植入物数量从25到1267不等,而在对照组中,植入物的数量范围为28至1450。植入物的放置与随访之间的时间为4-6个月至8年。结果表明,在2582个放置的植入物中,50例(1.94%)在接受BP治疗的患者中失败。这是在4050个放置的植入物中,188(4.6%)在非BP组中失败。荟萃分析的结果表明,BP治疗与植入物失败率增加显着相关(RR(95%CI)=1.73(1.03-2.83),p=0.04)。总的来说,本综述的定性评估表明,绝经后女性的BPs口服治疗不会增加牙种植失败率.因此,更大样本量的进一步研究应在牙种植体方面比较BP和非BP组.
    A systematic review was designed to investigate the effect of treatment with oral bisphosphonate (BP) on osseointegration of dental implants and the incidence of BP-related osteonecrosis of the jaw (BRONJ) in postmenopausal women. Multiple electronic databases, including MEDLINE (PubMed), EMBASE, and SCOPUS, were searched to find all eligible articles published since 1990. All titles and abstracts retrieved by searching information sources were evaluated independently by 2 authors against the eligibility criteria. The number of cases ranged from 11 to 235, and the number of controls ranged from 14 to 343. Alendronate was used in all other studies. Risedronate was used in 6 studies, while ibandronate was used in 4 studies. The number of implants in cases ranged from 25 to 1267, while in controls, the number of implants ranged from 28 to 1450. The time between the placement of implant and the follow-up visit ranged from 4-6 months to 8 years. The results show that out of 2582 placed implants, 50 (1.94%) failed in BP-treated patients. This is while out of 4050 placed implants, 188 (4.6%) failed in the non-BP group. The results from the meta-analysis demonstrated that BP therapy is significantly associated with increased implant failure rates (RR = 1.73 [95% CI, 1.03-2.83], P = .04). Overall, the qualitative assessment of this review suggests that oral treatment with BPs in postmenopausal women does not increase the rate of dental implant failure. Thus, further studies with larger sample sizes should compare BP and non-BP groups in regard to dental implants.
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  • 文章类型: Systematic Review
    系统评价旨在回答PICOS问题:“自体血小板浓缩物(APC)是预防和/或治疗有药物相关性颌骨坏死(MRONJ)风险/影响的患者的有效策略吗?”通过PubMed进行了文献检索,MEDLINE,EMBASE,和CINAHL(2006年1月-2023年9月)。包括30篇文章,评估预防(n=8*)和治疗策略(n=23*)。使用ROB-2,ROBIN-1和GRADE标准评估偏倚风险和研究质量。对符合条件的研究进行Meta分析。APC的应用在86.13%(p<0.001)的MRONJ预防中具有统计学意义,但在83.4%的MRONJ治疗中未能达到相同的确定性水平(p=0.08)。确定了高水平的偏见;因此,结果应谨慎解释.需要更多高质量的前瞻性随机对照试验来进一步评估APC在MRONJ管理中的有效性。
    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.
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  • 文章类型: Journal Article
    这项研究汇编了与药物相关的颌骨坏死(MRONJ)的病因有关的主要假设。对文献进行了叙述性回顾。MRONJ的病因是多因素的,尚未完全了解。主要假设考虑了抗再吸收药物引起的骨转换障碍。双膦酸盐和地诺单抗通过不同的作用机制抑制破骨细胞活性,积聚骨微骨折。其他假设也考虑口腔感染和炎症,双膦酸盐的抗血管生成作用和软组织毒性,和淋巴管生成的抑制作用。了解MRONJ的当前理论对于定义未来的研究和方案以最大程度地减少这种严重状况的发生率是必要的。
    This study compiles the main hypotheses involved in the etiopathogenesis of medication-related osteonecrosis of the jaw (MRONJ). A narrative review of the literature was performed. The etiopathogenesis of MRONJ is multifactorial and not fully understood. The main hypothesis considers the disturbance of bone turnover caused by anti-resorptive drugs. Bisphosphonates and denosumab inhibit osteoclast activity through different action mechanisms, accumulating bone microfracture. Other hypotheses also consider oral infection and inflammation, the antiangiogenic effect and soft tissue toxicity of bisphosphonates, and the inhibition of lymphangiogenesis. Knowledge of the current theories for MRONJ is necessary to define future studies and protocols to minimize the incidence of this severe condition.
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  • 文章类型: Journal Article
    本系统综述的目的是评估目前对药物相关性颌骨坏死的保守和手术治疗的有效性的认识。
    MEDLINE(PubMed),ScienceDirect和Cochrane图书馆的搜索与相关期刊的手工搜索相结合,包括2017年1月至2023年2月以英文发表的人类研究。包括评估药物相关性颌骨坏死(MRONJ)治疗策略的研究。质量和偏倚风险评估由JoannaBriggs研究所(JBI)偏倚风险工具进行评估。
    共筛选了4227篇文章,其中9项研究(7项队列研究和2项随机对照试验)符合纳入标准,并纳入最终数据综合。两项研究评估了保守方法治疗MRONJ的有效性,5项研究评估手术方法的有效性,2项研究比较了这些方法。随访时间6个月~60个月。根据偏见评估,纳入研究的平均JDI评分>9("低偏倚风险").疾病的阶段,介绍了对患者进行的手术和治疗结果.
    手术治疗似乎优于保守治疗,治疗不良阶段药物相关的颌骨坏死,而保守治疗似乎在疾病早期阶段的无症状患者中产生良好的结果。
    UNASSIGNED: The objective of this systematic review is to evaluate the current knowledge on the effectiveness of conservative and surgical treatment of medication-related osteonecrosis of the jaw.
    UNASSIGNED: MEDLINE (PubMed), ScienceDirect and Cochrane Library search in combination with hand-search of relevant journals was conducted including human studies published in English between January 2017 and February 2023. Studies assessing treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) were included. Quality and risk-of-bias assessment were evaluated by Joanna Briggs Institute (JBI) Risk of Bias tool.
    UNASSIGNED: A total of 4227 articles were screened from which 9 studies (7 cohort studies and 2 randomized controlled trials) met the inclusion criteria and were included in the final data synthesis. Two studies evaluate effectiveness of conservative approaches for treating MRONJ, 5 studies evaluate surgical approaches effectiveness, and 2 studies compare between those approaches. The follow-up period ranged from 6 months to 60 months. According to bias assessment, the mean JDI score of the included studies was > 9 (\"low risk of bias\"). The stage of the disease, the procedure performed on the patient and the results of the treatment were presented.
    UNASSIGNED: Surgical therapy seems to be superior to conservative therapy for the management of adverse stages medication-related osteonecrosis of the jaws, while conservative treatment appears to yield good outcomes at asymptomatic patients with early stages of the disease.
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  • 文章类型: Systematic Review
    目的:这篇综述旨在探讨荧光引导切除治疗坏死骨的疗效,并强调荧光在区分存活边缘和坏死边缘方面的重要性,以更有针对性和可预测地治疗MRONJ。
    方法:根据PRISMA指南使用PubMed,Scopus,和WebofScience数据库从2008年1月1日至2023年5月17日。进行具有以下关键字\"骨坏死\"和\"荧光\"的布尔搜索策略。然后,这些文章进行了筛选和资格阶段.包括有关在颌骨坏死患者中使用自体荧光引导激光治疗的论文。
    结果:通过电子搜索初步确定了320篇文章,最终,对17篇论文进行了定性分析。
    结论:结论:我们的发现表明,VELscope系统可以清晰地显示骨骼,使引导自发荧光精确,安全,可靠的技术。
    OBJECTIVE: This review aims to explore the efficacy of fluorescence-guided excision in the treatment of necrotic bone and highlights the importance of fluorescence in distinguishing viable margins from necrotic ones for a more targeted and predictable management of MRONJ.
    METHODS: The review was conducted according to PRISMA guidelines using PubMed, Scopus, and Web of Science databases from January 1, 2008, to May 17, 2023. The Boolean search strategy with the following keywords \"osteonecrosis\" AND \"fluorescence\" was performed. Then, the articles were subjected to screening and eligibility phases. The papers about the use of autofluorescence-guided laser therapy in patients with jaw osteonecrosis were included.
    RESULTS: A total of 320 articles were initially identified through an electronic search, and ultimately, 17 papers were included in the qualitative analysis.
    CONCLUSIONS: In conclusion, our findings demonstrate that the VELscope system allows for clear visualization of the bone, making guided autofluorescence a precise, safe, and reliable technique.
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  • 文章类型: Journal Article
    药物相关性颌骨坏死(MRONJ),抗吸收抗血管生成药物引起的严重副作用,特别是双膦酸盐(BPs),已成为一种具有挑战性的疾病,对患者的身心健康产生严重而深远的影响。虽然它发生频率高,而且有害,MRONJ的确切机制仍然未知,仍然缺乏系统和有针对性的方法。颌面外科医生专注于下颌骨和上颌骨骨坏死的病因以及对高危患者的适当口腔干预。适当的护理和药物治疗管理也至关重要。本文综述了BPs引起MRONJ的临床病理特征和研究现状。强调该疾病的潜在机制以及当前的治疗和预防策略。我们认为,对MRONJ潜在机制的深入理解将有助于开发更精确和有效的治疗方法,提高了患者的临床结局。
    Medication-related osteonecrosis of the jaw (MRONJ), a severe side effect caused by antiresorptive antiangiogenic medication, particularly bisphosphonates (BPs), has become a challenging disease with serious and profound effects on the physical and mental health of patients. Although it occurs with high frequency and is harmful, the exact mechanism of MRONJ remains unknown, and systematic and targeted approaches are still lacking. Maxillofacial surgeons focus on the etiology of osteonecrosis in the mandible and maxilla as well as the appropriate oral interventions for high-risk patients. Adequate nursing care and pharmacotherapy management are also crucial. This review provides a current overview of the clinicopathologic feature and research of MRONJ caused by BPs, with an emphasis on the potential mechanisms and current therapy and prevention strategies of the disease. We are of the opinion that an in-depth comprehension of the mechanisms underlying MRONJ will facilitate the development of more precise and efficacious therapeutic approaches, resulting in enhanced clinical outcomes for patients.
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  • 文章类型: Journal Article
    背景:探讨类风湿关节炎(RA)患者双膦酸盐相关性颌骨坏死(BAONJ)的发生。
    方法:考虑纳入评估BAONJ在RA患者(BAONJ-RA)中的发生的观察性研究。截至2022年12月,在六个数据库和灰色文献中进行了电子搜索。研究的选择,数据提取,并根据JoannaBriggs研究所关键评估清单对纳入的研究进行质量评估。采用分级方法对证据的确定性进行评价。
    结果:5项研究包括3项队列和2项横断面研究。RA患者的样本量为16至3201。一起,研究报告了36例BAONJ-RA。BAONJ-RA的患病率为0.094%至56.25%。发病率从0.4%到2.21不等。六到八岁之间的妇女受影响最大。阿仑膦酸盐(n=5)和唑来膦酸(n=9),口服和静脉注射,分别,是最常用的双膦酸盐。使用双膦酸盐的持续时间为2.7至8年。证据的确定性很低。
    结论:BAONJ-RA的发生率低。然而,对于这一结果,证据的确定性非常低.
    BACKGROUND: To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
    METHODS: Observational studies that evaluated the occurrence of BAONJ in individuals with RA (BAONJ-RA) were considered for inclusion. Electronic searches were performed up to December 2022 in six databases and in the grey literature. The study selection, data extraction, and quality assessment of the included studies according to the Joanna Briggs Institute Critical Appraisal Checklists was performed. The certainty of evidence was evaluated using the GRADE approach.
    RESULTS: Five studies were included three cohort and two cross-sectional. The sample size of subjects with RA ranged from 16 to 3201. Together, the studies presented 36 cases of BAONJ-RA. Prevalence of BAONJ-RA ranged from 0.094% to 56.25%. The incidence ranged from 0.4% to 2.21. Women between the 6th and 8th decade of life were the most affected. Alendronate (n=5) and zoledronic acid (n=9), orally and intravenously, respectively, were the most used bisphosphonates. The duration of bisphosphonates use ranged from 2.7 to 8 years. The certainty of evidence was very low.
    CONCLUSIONS: The occurrence of BAONJ-RA is low. However, the certainty of the evidence was very low for this outcome.
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