Department of Internal Medicine, University of Michigan, Ann Arbor.
SWOG Cancer Research Network Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, Washington.
JAMA Oncol. 2021 Feb 1;7(2):246-254. doi: 10.1001/jamaoncol.2020.6353.
Osteonecrosis of the jaw (ONJ) affects patients with cancer and metastatic bone disease (MBD) treated with bone-modifying agents (BMAs), yet the true incidence is unknown.
To define the cumulative incidence of ONJ at 3 years in patients receiving zoledronic acid for MBD from any malignant neoplasm.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective observational cohort study (SWOG Cancer Research Network S0702) included patients with MBD with either limited or no prior exposure to BMAs and a clinical care plan that included use of zoledronic acid within 30 days of registration. Medical, dental, and patient-reported outcome forms were submitted at baseline and every 6 months. Follow-up was 3 years. Osteonecrosis of the jaw was defined using established criteria. Data were collected from January 30, 2009, to December 13, 2013, and analyzed from August 24, 2018, to August 6, 2020.
INTERVENTIONS/EXPOSURES: Cancer treatments, BMAs, and dental care were administered as clinically indicated.
Cumulative incidence of confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for more than 8 weeks with no concurrent radiotherapy to the craniofacial region. Risk factors for ONJ were also examined.
The SWOG S0702 trial enrolled 3491 evaluable patients (1806 women [51.7%]; median age, 63.1 [range, 2.24-93.9] years), of whom 1120 had breast cancer; 580, myeloma; 702, prostate cancer; 666, lung cancer; and 423, other neoplasm. A baseline dental examination was performed in 2263 patients (64.8%). Overall, 90 patients developed confirmed ONJ, with cumulative incidence of 0.8% (95% CI, 0.5%-1.1%) at year 1, 2.0% (95% CI, 1.5%-2.5%) at year 2, and 2.8% (95% CI, 2.3%-3.5%) at year 3; 3-year cumulative incidence was highest in patients with myeloma (4.3%; 95% CI, 2.8%-6.4%). Patients with planned zoledronic acid dosing intervals of less than 5 weeks were more likely to experience ONJ than patients with planned dosing intervals of 5 weeks or more (hazard ratio [HR], 4.65; 95% CI, 1.46-14.81; P = .009). A higher rate of ONJ was associated with fewer total number of teeth (HR, 0.51; 95% CI, 0.31-0.83; P = .006), the presence of dentures (HR, 1.83; 95% CI, 1.10-3.03; P = .02), and current smoking (HR, 2.12; 95% CI, 1.12-4.02; P = .02).
As the findings show, the cumulative incidence of ONJ after 3 years was 2.8% in patients receiving zoledronic acid for MBD. Cancer type, oral health, and frequency of dosing were associated with the risk of ONJ. These data provide information to guide stratification of risk for developing ONJ in patients with MBD receiving zoledronic acid.
颌骨坏死（ONJ）影响接受骨修饰剂（BMA）治疗的癌症和转移性骨病（MBD）患者，但真实发病率尚不清楚。
定义接受唑来膦酸治疗 MBD 的患者在 3 年内发生 ONJ 的累积发生率，这些患者来自任何恶性肿瘤。
设计、地点和参与者：这项多中心前瞻性观察队列研究（SWOG 癌症研究网络 S0702）纳入了 MBD 患者，这些患者既往有限或无 BMA 暴露，且临床护理计划中包括在登记后 30 天内使用唑来膦酸。基线和每 6 个月提交一次医疗、牙科和患者报告的结果表格。随访时间为 3 年。颌骨坏死使用既定标准定义。数据于 2009 年 1 月 30 日至 2013 年 12 月 13 日收集，分析时间为 2018 年 8 月 24 日至 2020 年 8 月 6 日。
干预/暴露：根据临床需要给予癌症治疗、BMA 和牙科护理。
确诊 ONJ 的累积发生率，定义为上颌骨区域有暴露骨存在超过 8 周，且同期无颅面区域放射治疗。还检查了 ONJ 的风险因素。
SWOG S0702 试验纳入了 3491 例可评估患者（1806 名女性[51.7%]；中位年龄 63.1[范围 2.24-93.9]岁），其中 1120 例患有乳腺癌；580 例患有骨髓瘤；702 例患有前列腺癌；666 例患有肺癌；423 例患有其他肿瘤。2263 例患者进行了基线牙科检查（64.8%）。总体而言，90 例患者发生了确诊的 ONJ，1 年时的累积发生率为 0.8%（95%CI，0.5%-1.1%），2 年时为 2.0%（95%CI，1.5%-2.5%），3 年时为 2.8%（95%CI，2.3%-3.5%）；骨髓瘤患者的 3 年累积发生率最高（4.3%；95%CI，2.8%-6.4%）。计划唑来膦酸给药间隔小于 5 周的患者比计划给药间隔为 5 周或更长时间的患者更有可能发生 ONJ（风险比[HR]，4.65；95%CI，1.46-14.81；P=0.009）。更高的 ONJ 发生率与总牙齿数量较少（HR，0.51；95%CI，0.31-0.83；P=0.006）、佩戴义齿（HR，1.83；95%CI，1.10-3.03；P=0.02）和当前吸烟（HR，2.12；95%CI，1.12-4.02；P=0.02）相关。
研究结果显示，接受唑来膦酸治疗 MBD 的患者在 3 年后的 ONJ 累积发生率为 2.8%。癌症类型、口腔健康和给药频率与 ONJ 的风险相关。这些数据为指导接受唑来膦酸治疗的 MBD 患者发生 ONJ 的风险分层提供了信息。
