506 JADA 142(5) http://jada.ada.org May 2011 PRACTICE CLINICAL B isphosphonates (BPs) are drugs that effectively inhibit bone resorption, and they are recom- mended as an important compo- nent of treatment used to prevent skeletal complications in patients with metastases to the bone. 1,2 Despite the beneficial effects of BP in the treatment of metas- tases to the bone, these agents— particularly the more potent nitrogen-containing BPs pamid- ronate and zoledronic acid (ZOL)—are capable of causing osteonecrosis of the jaw (ONJ). 3,4 The true incidence of ONJ is unknown because most of the reported cases are from retrospec- tive analyses; the estimated inci- dence of ONJ in patients with cancer who received BP therapy for metastases to the bone ranges from 1 to 10 percent. 5-8 Although several risk factors for and associated comorbidities of BP-related ONJ (BRONJ) have been proposed, the exact patho- physiological mechanism has not been clarified fully; the type of BP, duration of the drug use and occurrence of tooth extractions or other invasive dental procedures Dr. Filippo Francini is a physician, Department of Odontostomatology and Maxillo-Facial Surgery, University of Siena, Italy. Dr. Pascucci is a physician, Medical Oncology Division, Department of Oncology, University of Siena, Italy. Dr. Edoardo Francini is a physician, Medical Oncology Division, Department of Oncology, University of Siena, Italy. Dr. Miano is a physician, Medical Oncology Division, Department of Oncology, University of Siena, Italy. Dr. Bargagli is a physician, Medical Oncology Division, Department of Oncology, University of Siena, Italy. Dr. Ruggiero is a physician, Department of Odontostomatology and Maxillo-Facial Surgery, University of Siena, Italy. Dr. Petrioli is a physician, Medical Oncology Division, Department of Oncology, University of Siena, Viale Bracci, 53100–Siena, Italy, email “r.petrioli@ ao-siena.toscana.it”. Address reprint requests to Dr. Petrioli. Osteonecrosis of the jaw in patients with cancer who received zoledronic acid and bevacizumab Filippo Francini, MD; Alessandra Pascucci, MD; Edoardo Francini, MD; Salvatora Tindara Miano, MD; Gianluca Bargagli, MD; Grazia Ruggiero, MD; Roberto Petrioli, MD ABSTRACT Background. The authors investigated the inci- dence of and risk factors for osteonecrosis of the jaw (ONJ) in patients with metastases to the bone who received the bisphosphonate agent zoledronic acid (ZOL) and chemotherapy combined with the antiangio- genic agent bevacizumab (BEV). Methods. The authors evaluated 59 participants (34 with breast cancer and 25 with nonsmall-cell lung cancer). All of the participants received 4 milligrams of ZOL via intravenous (IV) infusion every four weeks and 15 mg per kilogram of BEV every three weeks. They con- ducted a dental examination in participants at baseline and every three months until the patients died or were lost to follow-up. If needed, par- ticipants received periodontal disease treatment and underwent tooth extraction before they started receiving ZOL and BEV. Results. The median time the participants received ZOL therapy was 18.8 months (range, 3.1-28.9 months); 36 participants (61.0 percent) received ZOL therapy for more than one year. The median time partici- pants received BEV therapy was 16.7 months (range, 2.8-29.6 months). None of the participants required dentoalveolar surgery while under- going cancer treatment. After a median follow-up period of 19.7 months, none of the participants developed bisphosphonate-related ONJ. Conclusions and Clinical Implications. ZOL combined with BEV did not predispose to ONJ participants with cancer that had metastasized to the bone who underwent a baseline dental examination and preventive dental measures. The study results must be considered in the context of the study’s protocols and the follow-up period. Key Words. Bevacizumab; bisphosphonates; bone markers; bone metastases; osteonecrosis of the jaw; zoledronic acid. JADA 2011;142(5):506-513. J A D A C O N T I N U I N G E D U C A T I O N ✷ ✷ ® A R T I C L E 2