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Risk for Osteonecrosis of the Jaw After Treatment With Zoledronic Acid for Metastatic Bone Disease


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In an observational cohort study reported in JAMA Oncology, Catherine H. Van Poznak, MD, FASCO, and colleagues found that the 3-year incidence of osteonecrosis of the jaw was 2.8% among patients with cancer receiving zoledronic acid for metastatic bone disease. Shorter dosing interval, fewer teeth, use of dentures, and current smoking were associated with increased risk.

Catherine H. Van Poznak, MD, FASCO

Catherine H. Van Poznak, MD, FASCO

Study Details

The study included data on 3,491 patients with metastatic bone disease from the SWOG S0702 trial with either limited or no prior exposure to bone-modifying agents and a clinical care plan that included use of zoledronic acid within 30 days of registration. Among these patients, 1,120 had breast cancer, 580 had myeloma, 702 had prostate cancer, 666 had lung cancer, and 423 had another kind of neoplasm.

Medical, dental, and patient-reported outcome forms were collected at baseline and every 6 months. Patients were followed for 3 years. Osteonecrosis of the jaw was defined as an area of exposed bone in the maxillofacial region present for longer than 8 weeks in the absence of concurrent craniofacial region radiotherapy. Overall, a baseline dental exam was performed in 2,263 patients (64.8%).

Key Findings

The cumulative incidence of osteonecrosis of the jaw was 0.8% (95% confidence interval [CI] =0.5%–1.1%) at 1 year, 2.0% (95% CI = 1.5%–2.5%) at 2 years, and 2.8% (95% CI = 2.3%–3.5%) at 3 years. Cumulative incidence at 3 years was highest in patients with myeloma (4.3%) and lowest in those with breast cancer (2.4%).

Patients with less than 25 teeth (the median total number of teeth) (n = 1,142) had greater risk vs those with more than 25 teeth (n = 1,127), with 3-year incidence rates of 4.4% vs 2.4% (hazard ratio [HR] = 0.51, P = .006).

Risk was higher among patients with any dentures (n = 508, cumulative incidence = 5.0%) vs those with no dentures (n = 1,791, incidence = 2.9%; HR = 1.83, P = .02) and among those with removable dentures (n = 225, incidence = 6.5%) vs those with no removable dentures (n = 2,074, incidence = 3.0%; HR = 2.02, P = .03).

Risk was higher among patients with planned zoledronic acid dosing intervals of less than 5 weeks (n = 3,039, incidence = 3.2%) vs those with planned intervals of 5 weeks or longer (n = 447, incidence = 0.7%; HR = 4.65, P = .009).

Risk was higher among current smokers (n = 430, incidence = 3.7%) vs those who were not current smokers (n =1,548, incidence = 2.4%; HR = 2.12, P = .02).

The investigators concluded, “As the findings show, the cumulative incidence of osteonecrosis of the jaw after 3 years was 2.8% in patients receiving zoledronic acid for metastatic bone disease. Cancer type, oral health, and frequency of dosing were associated with the risk of osteonecrosis of the jaw. These data provide information to guide stratification of risk for developing osteonecrosis of the jaw in patients with metastatic bone disease receiving zoledronic acid.”

Dr. Van Poznak, of the Department of Internal Medicine, University of Michigan, Ann Arbor, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the National Cancer Institute and Novartis International AG. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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