Incidence and Risk Factors of Osteonecrosis of the Jaw in Advanced Cancer Patients after Treatment with Zoledronic Acid or Denosumab: A Retrospective Cohort Study

• Published in: Biological & pharmaceutical bulletin Vol. 38; no. 12; pp. 1850 - 1855
• Main Authors: Kajizono, Makoto, Sada, Hikaru, Sugiura, Yuhko, Soga, Yoshihiko, Kitamura, Yoshihisa, Matsuoka, Junji, Sendo, Toshiaki
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.12.2015
• Subjects: Aged; Anemia - complications; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Bone Diseases - etiology; Bone Diseases - prevention & control; denosumab; Denosumab - adverse effects; Denosumab - therapeutic use; Dental Care; Diabetes Complications; Diphosphonates - adverse effects; Diphosphonates - therapeutic use; Female; Humans; Imidazoles - adverse effects; Imidazoles - therapeutic use; Incidence; Jaw - drug effects; Jaw - pathology; Logistic Models; Male; medication-related osteonecrosis of the jaw (MRONJ); Middle Aged; Neoplasms - complications; Odds Ratio; Osteonecrosis - chemically induced; Osteonecrosis - epidemiology; Osteonecrosis - prevention & control; periodical dentistry maintenance; Retrospective Studies; Risk Factors; zoledronic acid
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b15-00385

Zoledronic acid and denosumab are two antiresorptive drugs currently in use for treating osteoporosis. They have different mechanisms of action, but both have been shown to delay the onset of skeletal-related events in patients with advanced cancer. However, medication-related osteonecrosis of the jaw (MRONJ) has been reported in cancer patients treated with zoledronic acid or denosumab. We studied 155 patients with several types of advanced cancer who were treated with zoledronic acid or denosumab in our hospital during the period from April 2010 through March 2013. Thirteen of these 155 patients (8.4%) developed MRONJ. MRONJ development was significantly associated with the number of zoledronic acid or denosumab infusions (p<0.001) and the duration of zoledronic acid or denosumab therapy (p<0.001). Logistic regression analysis showed that diabetes [odds ratio (OR)=6.699, 95% confidence interval (CI), 1.435–31.277, p=0.016], anemia [OR=14.559, 95% CI, 2.161–98.069, p=0.006], and pus discharge [OR=6.491, 95% CI, 1.514–27.835, p=0.012] significantly increased the risk of developing MRONJ. However, the risk of MRONJ was significantly lower [OR=0.137, 95% CI, 0.020–0.944, p=0.043] when patients received periodical dentistry maintenance. Diabetes, anemia, and pus discharge may also play roles in its development. These findings suggest that the active inclusion of dentistry maintenance in bisphosphonate or denosumab treatment of cancer patients can reduce MRONJ development.