Replacing zoledronic acid with denosumab is a risk factor for developing osteonecrosis of the jaw

Publication date: Available online 6 March 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Tomoko Higuchi, Yoshihiko Soga, Misato Muro, Makoto Kajizono, Yoshihisa Kitamura, Toshiaki Sendo, Akira Sasaki
ObjectiveIntravenous zoledronic acid (ZA) is often replaced with subcutaneous denosumab in bone metastatic cancer patients. Despite their different pharmacological mechanisms of action, both denosumab and ZA are effective in bone metastasis but have osteonecrosis of the jaw (ONJ) as a side effect. ZA persists in the body almost indefinitely, while denosumab does not persist for long periods. This study evaluated the risks of developing ONJ when replacing ZA with denosumab.Study DesignA total of 161 Japanese patients administered ZA for bone metastatic cancer were enrolled in this single-center, retrospective, observational study. The risk of developing ONJ was evaluated by logistic regression analysis using the following factors: age, sex, cancer type, angiogenesis inhibitors, steroids, and replacement of ZA with denosumab.ResultsSeventeen patients (10.6%) developed ONJ. Multiple regression analysis indicated a significant difference in rate of ONJ associated with replacement of ZA with denosumab (OR = 3.81, 95% CI: 1.04 – 13.97, P = 0.043).ConclusionReplacing ZA with denosumab is a risk factor for developing ONJ. Both bisphosphonate binding to the bone and RANKL inhibition could additively increase the risk of developing ONJ. We bring the replacement of ZA with denosumab to the attention of clinical oncologists.



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