Yoshimura Hitoshi, Ohba Seigo, Yoshida Hisato, Saito Kyoko, Inui Kazuyoshi, Yasui Rie, Ichikawa Dai, Aiki Minako, Kobayashi Junichi, Matsuda Shinpei, Imamura Yoshiaki, Sano Kazuo
Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Department of Regenerative Oral Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan.
Oncol Lett. 2017 Jul;14(1):127-136. doi: 10.3892/ol.2017.6121. Epub 2017 May 4.
Denosumab, a human monoclonal antibody directed against the receptor activator of nuclear factor-κβ ligand (RANKL), is used for the treatment of patients with metastatic cancer of the bone or osteoporosis. Recent reports have demonstrated that denosumab can induce osteonecrosis of the jaw (ONJ), but reported cases of this are uncommon. The present study reports the case of an 86-year-old male with prostate cancer patient exhibiting bone metastases who developed ONJ whilst receiving denosumab. To elucidate the influence of denosumab on the development of ONJ, the present study also reviewed the literature, including clinical trials and case reports. In the clinical trials, the prevalence of denosumab-related ONJ was higher in patients with cancer compared with those with osteoporosis. The high risk of ONJ in patients with cancer was thought to be associated with the differing dose and frequency of denosumab administration. The prevalence of ONJ was not significantly different between patients receiving denosumab and bisphoshonate (BP). In the reported cases, denosumab-related ONJ had a similar clinical presentation to BP-related ONJ. There was also a tendency for denosumab-related ONJ to develop in the mandible of elderly patients. Previous invasive dental treatment was a commonly shared characteristic of patients with denosumab-related ONJ. A complex medical history was also suspected to affect the prevalence. No clear association between the dose or duration of denosumab treatment and the development of ONJ was observed. Although conservative treatments are given for denosumab-related ONJ, non-improving cases were managed surgically with primarily positive results. Because denosumab may offer superior results compared with BP for the treatment of metastatic cancer of the bone or osteoporosis, the use of denosumab is expected to increase in the near future. Clinicians should also be aware of the risk factors for denosumab-related ONJ, in order to aid in its diagnosis. In addition, patients treated with denosumab should receive prophylactic treatment to maintain their oral health prior to, during and after denosumab treatment.
地诺单抗是一种针对核因子κB受体活化因子配体(RANKL)的人源单克隆抗体,用于治疗骨转移癌或骨质疏松症患者。近期报告显示,地诺单抗可诱发颌骨坏死(ONJ),但此类报告病例并不常见。本研究报告了一例86岁前列腺癌伴骨转移患者在接受地诺单抗治疗时发生ONJ的病例。为阐明地诺单抗对ONJ发生发展的影响,本研究还回顾了相关文献,包括临床试验和病例报告。在临床试验中,与骨质疏松症患者相比,癌症患者中与地诺单抗相关的ONJ患病率更高。癌症患者发生ONJ的高风险被认为与地诺单抗给药剂量和频率的差异有关。接受地诺单抗治疗的患者与接受双膦酸盐(BP)治疗的患者之间ONJ患病率无显著差异。在报告的病例中,与地诺单抗相关的ONJ临床表现与与BP相关的ONJ相似。与地诺单抗相关的ONJ也有在老年患者下颌骨发生的倾向。既往侵入性牙科治疗是与地诺单抗相关的ONJ患者的一个共同特征。复杂的病史也被怀疑会影响患病率。未观察到地诺单抗治疗剂量或疗程与ONJ发生之间存在明确关联。尽管对与地诺单抗相关的ONJ采取了保守治疗,但对于无改善的病例进行了手术处理,主要取得了阳性结果。由于在治疗骨转移癌或骨质疏松症方面,地诺单抗可能比BP疗效更佳,预计在不久的将来地诺单抗的使用将会增加。临床医生也应了解与地诺单抗相关的ONJ的危险因素,以协助诊断。此外,接受地诺单抗治疗的患者在治疗前、治疗期间和治疗后应接受预防性治疗以保持口腔健康。