Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy.
Department of Periodontology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, 3010, Bern, Switzerland.
Clin Oral Investig. 2018 Mar;22(2):597-615. doi: 10.1007/s00784-017-2325-6. Epub 2018 Jan 13.
The most debated topic about medication-related osteonecrosis of the jaws (MRONJ) is its therapy, as there are no definitive guidelines. The aims of this systematic review were (a) to outline the best therapeutic approach according to the stage at diagnosis and (b) to perform a meta-analysis to assess whether the drug-holiday protocol may be or not an effective method in the management of MRONJ patients.
The systematic review was performed following the PRISMA principles. Results were screened according to inclusion and exclusion criteria regarding staging before/after treatment, follow-up, and information provided by the authors. For statistical analysis, linear variables are reported as means and standard deviations, medians, and inter-quartile range (IQR); normality of data, according to the distribution of complete healing (primary outcome variable), was assessed with the Kolmogorov-Smirnov test. A p value < 0.05 was considered statistically significant for all tests.
Thirteen studies were selected out of 1480. None of them was case-controlled or randomized. Conservative approach showed good results at early stages, but heterogeneous result at advanced stages (100% stage 0, stage I range 81-97%, stage II range 63.6-100%, stage III 73%). Surgical approach showed heterogeneous results at all stages (stage I range 0-100%, stage II range 52-100%, stage III range 50-100%). Statistical analysis showed a significantly higher prevalence of completely healed sites in patients who followed the drug-holiday protocol.
The results suggest that the current stage-specific approach for MRONJ therapy is based on a sound clinical rationale. Conservative treatment appears to yield better outcomes at early stages, while further investigations are needed to elucidate the best protocols for the management of advanced stages. The drug-holiday protocol statistically promotes complete healing after oral surgery procedures but the application should be dictated by the condition of each patient.
At present, early MRONJ stages should be primarily treated by means of a conservative approach while more advanced stages must be carefully evaluated. Individual decisions should be made for every single case even with respect to the drug-holiday protocol.
关于药物相关性颌骨坏死（MRONJ），最具争议的话题是其治疗方法，因为目前尚无明确的指导方针。本系统评价的目的是（a）根据诊断时的阶段概述最佳治疗方法，（b）进行荟萃分析以评估药物假期方案是否可能是管理 MRONJ 患者的有效方法。
本系统评价遵循 PRISMA 原则进行。根据治疗前后分期、随访和作者提供的信息，通过纳入和排除标准筛选结果。对于统计分析，线性变量以平均值和标准差、中位数和四分位距（IQR）报告；根据完全愈合的分布（主要结局变量）评估数据的正态性，采用 Kolmogorov-Smirnov 检验。所有检验均以 p 值<0.05 为具有统计学意义。
从 1480 篇文章中筛选出 13 篇研究。没有一项是病例对照或随机对照研究。保守治疗在早期阶段效果良好，但在晚期阶段结果不一致（0 期 100%，I 期范围 81-97%，II 期范围 63.6-100%，III 期 73%）。手术治疗在所有阶段的结果均不一致（I 期范围 0-100%，II 期范围 52-100%，III 期范围 50-100%）。统计分析显示，遵循药物假期方案的患者中完全愈合部位的发生率明显更高。
结果表明，目前针对 MRONJ 治疗的特定阶段方法基于合理的临床原理。保守治疗在早期阶段似乎产生更好的结果，而需要进一步研究阐明管理晚期阶段的最佳方案。药物假期方案在口腔手术后促进完全愈合，但应用应根据每位患者的情况决定。
目前，早期 MRONJ 阶段应主要采用保守方法治疗，而更晚期阶段则必须仔细评估。即使是药物假期方案，也应针对每个病例做出个体化决策。
