Incidence rate of osteonecrosis of jaw after cancer treated with bisphosphonates and denosumab: A systematic review and meta‑analysis

• Published in: Special care in dentistry Vol. 44; no. 2; pp. 530 - 541
• Main Authors: Zhang, Chengrong, Shen, Guoshuang, Li, Huihui, Xin, Yuanfang, Shi, Mingqiang, Zheng, Yonghui, Wang, Miaozhou, Liu, Zhen, Zhao, Yi, Zhao, Fuxing, Ren, Dengfeng, Zhao, Jiuda
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-03-2024
• Subjects: adjuvant treatment; Bisphosphonate-Associated Osteonecrosis of the Jaw - epidemiology; Bisphosphonates; Bone cancer; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; bone metastases; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; Cancer; Clinical trials; denosumab; Denosumab - adverse effects; Denosumab - therapeutic use; Diphosphonates - adverse effects; Diphosphonates - therapeutic use; Drug administration; Humans; Incidence; Jaw; Metastases; Necrosis; Osteonecrosis; osteonecrosis of the jaw; Prostate cancer; Quality of life; Solid tumors; Zoledronic acid; osteonecrosis of the jaw; zoledronic acid; bone metastases; bisphosphonates; cancer; adjuvant treatment; denosumab
• ISSN: 0275-1879; 1754-4505; 1754-4505
• DOI: 10.1111/scd.12877

Objectives
This study aimed to assess the overall incidence of osteonecrosis of the jaw (ONJ) caused by bisphosphonates and denosumab when used for controlling bone cancer metastasis or as adjuvant therapy.
Subjects and Methods
A systematic search of the PubMed, Embase, and Cochrane Library databases and major meetings’ proceedings as of July 30, 2022, identified randomized controlled trials (RCTs) and observational trials that evaluated ONJ caused by denosumab or bisphosphonates. The total incidence and risk ratio (RR) for ONJ were calculated using a random‐effects model.
Results
A total of 42 003 patients with various solid tumors reported in 23 RCTs were included. The overall ONJ incidence in cancer patients receiving denosumab or bisphosphonates was 2.08% (95% CI 1.37–2.91; p < .01; I2 = 94.99%). Patients receiving denosumab had a higher ONJ incidence than those receiving bisphosphonates (RR 1.64, 95% CI 1.10–2.44; p < .05; I2 = 65.4%). Subgroup analyses showed that prostate cancer patients receiving denosumab and receiving zoledronic acid had the highest ONJ incidences, 5.0% and 3.0%, respectively. The incidence of ONJ induced by different doses was also different.
Conclusions
The incidence of ONJ caused by denosumab and bisphosphonates is low, the dose of the drug and the type of cancer have certain influence on ONJ. Therefore, clinicians should use the drug reasonably to improve the quality of life of patients.