Use of Radium-223 Dichloride in Patients With Osteonecrosis of the Jaw Induced by Zoledronic Acid: Report of 2 Cases

Bisphosphonates, a group of inorganic pyrophosphate analogues that prevent the loss of bone density, are commonly used in patients with bone metastases; the calcium-mimetic a-emitter radium-223 dichloride (Ra223) is a bone-targeting therapy used in patients with metastatic castration-resistant prostate cancer (mCRPC)-related bone metastases. Both treatments reduce pain and disability; Ra223 is associated with significantly improved overall survival in mCRPC. Patients who receive bisphosphonate therapy are at risk of developing osteonecrosis of the jaw, especially in those who do not undergo an accurate oral evaluation and sanitation before the beginning of therapy, and in patients who present with conditions that facilitate the development of this problem, such as inadequate oral and dental care, lack of prophylactic antimicrobial mouth rinsing, patient comorbidity, or suboptimal suturing after tooth extraction. Although there is possible synergism between bisphosphonates and Ra223 therapy, there is no consensus about the use of Ra223 in patients with previous/current osteonecrosis of the jaw induced by zoledronic acid. However, our experience suggests that Ra223 therapy might not be contraindicated in patients with osteonecrosis of the jaw induced by zoledronic acid if an appropriate multidisciplinary approach is followed, and we report 2 cases of patients with current or previous osteonecrosis of the jaw induced by zoledronic acid, who were treated with Ra223 for mCRPCrelated bone metastases. Multidisciplinary management, including accurate clinical and radiological evaluation before beginning therapy with Ra223, together with oral sanitation and periodic controls during treatment, allowed successful administration of Ra223 while reducing side effects, with absent or minimal worsening of osteonecrosis.