Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient’s quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

摘要 引言 药物相关性颌骨骨髓炎（medication-related osteonecrosis of the jaws）是抗吸收治疗与抗血管生成治疗引发的严重并发症，临床治疗手段有限，对患者生活质量影响显著。研究目的：本研究旨在评估接受双膦酸盐（bisphosphonate）治疗的肿瘤患者中，与药物相关性颌骨骨髓炎相关的危险因素；此外，本研究还检测了唾液白细胞介素-6（interleukin-6，IL-6）水平，以探讨其与药物相关性颌骨骨髓炎严重程度及发病风险的关联。研究方法：本研究为病例对照研究，纳入74例实体瘤及多发性骨髓瘤骨转移患者。将患者分为三组：① 接受双膦酸盐治疗且并发药物相关性颌骨骨髓炎者；② 接受双膦酸盐治疗但未并发药物相关性颌骨骨髓炎者；③ 曾接受双膦酸盐预处理者。收集患者的人口学与临床资料以评估相关危险因素；通过临床检查确诊药物相关性颌骨骨髓炎，并采集未刺激唾液样本以定量检测IL-6水平。研究结果：结果显示，确诊药物相关性颌骨骨髓炎的患者接受的双膦酸盐疗程更长、给药剂量更高（p=0.001），且采用每月输注方案（p=0.044；优势比OR=7.75）。在双膦酸盐治疗期间未接受专科牙医常规随访的患者，以及吸烟患者，发生药物相关性颌骨骨髓炎的风险显著升高（分别对应p=0.019；OR=8.25与p=0.031；OR=9.37）。第一组患者同时接受化疗、糖皮质激素联合双膦酸盐治疗以及牙科手术操作的比例更高，但该差异无统计学意义（p=0.129）。各组间唾液IL-6水平无统计学差异（p=0.571），且其水平与药物相关性颌骨骨髓炎的严重程度无关联（p=0.923）。研究结论：本研究发现，双膦酸盐治疗周期更长、采用每月输注方案、未接受口腔健康维护的专科牙科随访以及吸烟，均与药物相关性颌骨骨髓炎的发生相关。双膦酸盐治疗期间的专科牙科随访，已被证实是预防该并发症的重要保护因素。