Frequent zoledronic acid use, other factors increase risk for osteonecrosis of the jaw
Patients with cancer who received zoledronic acid for metastatic bone disease appeared at higher risk for osteonecrosis of the jaw if they had more frequent exposure to the agent, poor oral health or currently smoked, study results showed.
Researchers also observed higher rates of osteonecrosis of the jaw — a painful condition that can make eating, speaking and smiling difficult — among patients with multiple myeloma compared with other malignancies.
“Osteonecrosis of the jaw, also called medication-related osteonecrosis of the jaw, is a clinically relevant problem affecting patients treated with bisphosphonates, denosumab and/or antiangiogenic therapy,” Catherine Van Poznak, MD, FASCO, associate professor in the department of internal medicine at University of Michigan, Ann Arbor, told Healio. “At the time when SWOG Cancer Research Network S0702 was designed, the incidence of osteonecrosis of the jaw in patients with metastatic bone disease was not known.”
For the multicenter, prospective, observational cohort study, published in JAMA Oncology, investigators sought to evaluate cumulative incidence of osteonecrosis of the jaw at 3 years and associated risk factors for developing the condition among 3,491 patients (median age, 63.1 years; range, 22.4-93.9; 51.7% women; 86.8% white) with metastatic bone disease treated with zoledronic acid. About one-third of patients (n = 1,120) had breast cancer, followed by prostate cancer (n = 702), lung cancer (n = 666), multiple myeloma (n = 580) and other neoplasms (n = 423).
Patients had limited or no prior exposure to bone-modifying agents and a clinical care plan that included zoledronic acid use within 30 days of registration. Dental, medical and patient-reported outcome forms were provided at baseline and every 6 months, with data collection occurring between Jan. 30, 2009, and Dec. 13, 2013.
Researchers defined cumulative incidence of osteonecrosis of the jaw as an area of bone exposed in the maxillofacial region present for longer than 8 weeks with no concurrent radiotherapy to the craniofacial region.
Median follow-up was 3 years (range, 2-3.1) among patients still alive at last contact.
According to study results, 90 patients developed confirmed osteonecrosis of the jaw, for a cumulative incidence of 0.8% (95% CI, 0.5-1.1) at 1 year, 2% (95% CI, 1.5-2.5) at 2 years and 2.8% (95% CI, 2.3-3.5) at 3 years.
Researchers observed higher incidence among patients with planned zoledronic acid dosing intervals of less than 5 weeks compared with intervals of 5 weeks or more (HR = 4.65; 95% CI, 1.46-14.81).
Patients with multiple myeloma had the highest 3-year cumulative incidence (4.3%; 95% CI, 2.8-6.4), whereas patients with breast cancer had the lowest incidence (2.4%; 95% CI, 1.5-3.4).
Three-year cumulative incidence also was higher among those who received a baseline dental exam (64.8%) vs. those who did not (3.4% vs. 1.9%; HR = 1.67; 95% CI, 1.02-2.75). Factors associated with a higher likelihood of not having a baseline dental exam included Black race, nonuse of alcohol and current smoking status.
Other factors associated with higher rates of osteonecrosis of the jaw included the presence of dentures (HR = 1.83; 95% CI, 1.1-3.03) and current smoking status (HR = 2.12; 95% CI, 1.12-4.02). Patients with a total number of teeth at baseline greater than the median of 25 had a lower incidence of osteonecrosis of the jaw than those with fewer teeth (HR = 0.51; 95% CI, 0.31-0.83).
Among 460 patients who reported use of the bone-modifying agent denosumab, 11 had confirmed osteonecrosis of the jaw, for a 3-year cumulative incidence of 3.2% (95% CI, 1.8-5.1). Moreover, patients who reported receiving antiangiogenic therapy within 1 year after registration had higher cumulative incidence of osteonecrosis of the jaw after 1 year (4.9%; 95% CI, 3.2-7.2) than those who did not receive antiangiogenic therapy (2.5%; 95% CI, 1.8-3.4).
Those with osteonecrosis of the jaw reported worse oral health-associated quality of life at the time of diagnosis, with a mean pain score at the time of diagnosis of 2.72 compared with 0.64 among those who did not develop the condition (P < .001).
Limitations of the study included a lack of detailed data on antiangiogenic agents, sequence of therapy, additional supportive therapies and socioeconomic data, such as dental insurance, income or education level.
Future research within SWOG Cancer Research Network S0702 includes additional analysis of the data and materials collected on study, Van Poznak said.
“Identification of those at greater risk for osteonecrosis of the jaw could be used to design studies targeting prevention strategies in the high-risk population,” she said. “Our findings can be used by clinicians to counsel patients on their risks for developing osteonecrosis of the jaw, as well as possibly impact decisions on dosing intervals of zoledronic acid.”
For more information:
Catherine Van Poznak, MD, FASCO, can be reached at University of Michigan, 500 S. State St., Ann Arbor, MI 48109; email: cvanpoz@med.umich.edu.
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