药物相关性颌骨坏死 (MRONJ) 与多发性骨髓瘤患者的 eNOS 多态性：单中心经验。
Medication-related osteonecrosis of the jaw (MRONJ) and eNOS Polymorphisms in multiple myeloma patients: a single center experience.
机构信息
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Gaziantep University, Gaziantep, Turkey.
Department of Hematology, Istanbul Training and Research Hospital, University of Health Sciences, Org. Nafiz GURMAN Cad. 34098 Fatih, Istanbul, Turkey.
出版信息
BMC Oral Health. 2021 May 18;21(1):272. doi: 10.1186/s12903-021-01634-9.
BACKGROUND
Multiple myeloma (MM) constitutes approximately 10% of hematological malignancies. Bisphosphonates have established themselves in solid organ metastasis and multiple myeloma lytic bone lesions by inhibiting osteoclast activation. Medication-related osteonecrosis of the jaw (MRONJ) emerges as an important complication. Investigating host-based factors, and developing personal risk factors gain importance in the development mechanism of MRONJ. We aimed to reveal the different genotype polymorphisms, and clinical effects of eNOS in patients with a diagnosis of MRONJ in MM patients.
METHODS
Medical records and blood samples were collected from 60 MRONJ patients with MM and 60 healthy controls. Inclusion criteria was having an exposed maxillofacial bone for more than eight weeks, a history of bisphosphonates, and no history of radiation therapy for the jaws. eNOS G894T and intron 4 VNTR were calculated by polymerase chain reaction and/or restriction fragment length polymorphism.
RESULTS
eNOS G894T and VNTR genotypes and alleles were compared statistically with the healthy control group. There was no significant difference between the two groups. In comparison between G894T and clinical parameters, aphthous stomatitis was more common in TT genotype, while DMFT > 3 was more common in TG-GG genotype (p = 0.035, 0.023).
CONCLUSIONS
eNOS induces osteogenesis in bone metabolism, with its regulatory effects on bone remodeling and also NO induced angiogenesis takes place indirectly with its protective effect on endothelial functions. We see that these polymorphisms affecting the entire process of bone remodeling and angiogenesis, especially mucosal damage, which is the triggering factor of MRONJ pathology, have been revealed in the MM patient group. Considering the MRONJ initiating factors, it is necessary to emphasize the importance of our study results. It should be seen as an important step for new studies towards MRONJ and its treatment.
背景
多发性骨髓瘤（MM）约占血液系统恶性肿瘤的 10%。双膦酸盐通过抑制破骨细胞的激活，在实体器官转移和多发性骨髓瘤溶骨性骨病变中得到了确立。药物相关的下颌骨坏死（MRONJ）是一种重要的并发症。研究宿主相关因素和开发个体危险因素在 MRONJ 的发病机制中变得越来越重要。我们旨在揭示不同基因型多态性和 eNOS 在 MM 患者 MRONJ 患者中的临床作用。
方法
收集 60 名 MM 伴 MRONJ 患者和 60 名健康对照者的病历和血样。纳入标准为颌面部骨暴露超过 8 周，有双膦酸盐治疗史，无颌骨放射治疗史。通过聚合酶链反应和/或限制性片段长度多态性计算 eNOS G894T 和内含子 4VNTR。
结果
eNOS G894T 和 VNTR 基因型和等位基因与健康对照组进行统计学比较。两组间无显著性差异。在 G894T 与临床参数的比较中，TT 基因型中口疮性口炎更为常见，而 TG-GG 基因型中 DMFT>3 更为常见（p=0.035，0.023）。
结论
eNOS 诱导骨代谢中的成骨作用，其对骨重塑的调节作用以及通过对内皮功能的保护作用间接发生的 NO 诱导的血管生成。我们发现这些多态性影响了骨重塑和血管生成的整个过程，特别是黏膜损伤，这是 MRONJ 病理的触发因素，在 MM 患者组中得到了揭示。考虑到 MRONJ 的起始因素，必须强调我们研究结果的重要性。这应该被视为针对 MRONJ 及其治疗的新研究的重要步骤。
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