AAOMS position paper on MRONJ (2022 update)

Position paper下载:AAOMS.org/MRONJ. (曾经介绍过2014版的position paper

与2014版相比,重要变化如下(按照文章阅读顺序进行记录):

  1. 2014版对导致MRONJ的药物介绍包括双膦酸盐类(静滴/口服)、RANK 配体抑制剂(denosumab——地诺单抗/地舒单抗(普罗力(Prolia),安加维(Xgeva))和抗血管生成药;更新后的position paper删除了抗血管生成药,paper认为双膦酸盐类药物作为导致MRONJ危险因子的证据是充足的,而抗血管生成药、皮质类固醇以及免疫调节剂这类药物导致MRONJ的证据不足,一些研究报道的抗骨吸收药物与抗血管生成药物的协同作用主要是基于个案报道以及小样本调查,也缺乏足够的证据支持:
  2. paper认为既往使用按照治疗时长计算的抗骨吸收药物的使用总量与发生MRONJ之间的关系也是难以证实的;可能需要使用如累积药物剂量来重新进行调查;
  3. 抗骨吸收药物除了2014版中的双膦酸盐类、denosumab外,介绍了一种新药Romosozumab,这是一种预防骨质疏松妇女发生骨折的单抗药物,通过Wnt通路发挥作用;
  4. 基于1中的变化,Case definition对于用药史的描述也发生了变化,2014版是“现/曾使用抗骨吸收药物或抗血管生成药物”;更新版本为“现/曾单独,或与免疫调节剂或抗血管生成药物共同使用抗骨吸收药物”;
  5. MRONJ分期的变化不大,Stage 0 (Nonexposed bone variant)的临床表现中,2014有一条是“无法用牙髓坏死解释的根尖周/牙周窦道”,2022版将这条改为“口内外肿胀”;
  6. 与1对应,2022版在导致MRONJ的药物相关性风险因子中认为,除了抗骨吸收药物外,其他药物导致MRONJ的证据不足,这些其他药物导致MRONJ的证据等级为5级(即基于分散的个案报道以及小样本病例(小于5例)),不足采信;
  7. 2022版中采用新的研究数据表明在骨质疏松的患者中,RANK-L抑制剂导致MRONJ的风险为0.3%,比使用双膦酸盐的这类患者高了一个数量级(0.02-0.05%);而在2014版中认为这两者差不多的;
  8. 在使用新药Romosozumab治疗骨质疏松的患者中,MRONJ发生略与双膦酸盐差不多,为0.05-0.05%‘
  9. 2022版增加了在非恶性骨病中MRONJ的内容,及儿童人群中MRONJ发生几率的内容;
  10. 与2对应,在风险因素介绍中,2022版认为在使用抗骨吸收药物或denosumab的癌症患者中,用药时长与MRONJ之间之间是有正相关的,但是在骨质疏松患者中,这方面的报道是混乱的,所以认为用药时长在骨质疏松患者发生MRONJ中可能是一个风险因子,但是总体风险很低;
  11. 数据更新,如2022版中,使用BPs(双膦酸盐类药物)暴露的骨质疏松患者拔牙后发生MRONJ的几率为0-0.15%,而在使用denosumab的骨质疏松患者中约为1%;在使用BPs的癌症患者中,拔牙后发生MRONJ的几率据报道为1.6-14.8%;
  12. 关于drug holiday,2014版中对于口服BPs的患者,尤其是使用时间>4年的高风险患者,认为可以停药2个月,而在2022版中对此未达成共识,故无推荐;而在使用denosumab的患者中,推荐的是停药3-4个月后可进行牙槽手术治疗,术后6-8周可继续使用,以降低停药后骨折风险;2022版总体认为"It is clear the benefit of fracture prevention outweighs the risk of MRONJ development in osteoporotic patients. This benefit is even more favorable in the cancer population where bone-stabilizing medications significantly improve quality of life, and it is detrimental when antiresorptives are withheld due to MRONJ safety concerns."
  13. 2014版中的治疗是按照分期进行的,2022版中将治疗方式分为预防、非手术治疗以及手术治疗三类,然后再按照恶性肿瘤/非恶性肿瘤患者治疗前和治疗中的预防、非手术治疗的分期治疗应用、下颌骨病变的分期手术治疗、上颌骨病变的分期手术治疗进行介绍。

以下内容来自2022版:

  • MRONJ Prevention Strategies
Pretherapy (nonmalignant disease) Pretherapy (malignant disease) During antiresorptive therapy (nonmalignant disease) During antiresorptive therapy/targeted therapies (malignant disease)
1. Educate patient about the potential risks associated with long-term ART[1].
2. Optimization of dental health can occur concurrent with ART.
1. Educate patients about the higher risk of MRONJ and the importance of regimented dental care.
2. Optimization of the dental health prior to the initiation of ART if systemic conditions permit (extraction of nonrestorable teeth or teeth with a poor prognosis).
1. No alteration of operative plan for most patients.
2. Considerations include drug schedule, duration of therapy, comorbidities, other medications (especially chemotherapy, steroids or antiangiogenics), degree of underlying infection/inflammation and extent of surgery to be performed. Drug holidays are controversial.
3. BTM[2] are not a useful tool to assess MRONJ risk.
1. Educate patients about the higher MRONJ risk in the setting of malignant disease.
2. Educate the patient about the importance of regimented dental care and prevention.
3. Avoid dentoalveolar surgery if possible.
4. Consider root retention techniques to avoid extractions. Dental implants are contraindicated. Drug holidays are controversial.
  • Initial evaluation

initial_evaluation_2022_position_paper

  • Non-operative therapies

non-operative_therapies_2022_position_paper

  • Operative therapies for mandibular disease

operative_therapies_for_mandibular_disease_2022_position_paper

  • Operative therapies for maxillary disease

operative_therapies_for_maxillary_disease_2022_position_paper

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