Predictive factors for ONJ risk with zoledronic acid identified
medwireNews: The risk for osteonecrosis of the jaw (ONJ) following zoledronic acid treatment in patients with bone metastases is associated with cancer type, oral health, and dosing frequency, US researchers report.
These findings “should help to guide stratification of risk for developing ONJ in patients receiving zoledronic acid,” write Catherine Van Poznak (University of Michigan, Ann Arbor) and fellow researchers in JAMA Oncology.
In an analysis of 3491 participants of the prospective, observational SWOG S0702 study of the bisphosphonate zoledronic acid for bone metastases, 90 patients developed confirmed ONJ, defined as an area of exposed bone in the maxillofacial region present for a minimum of 8 weeks with no concurrent radiotherapy to the craniofacial region. The 1-, 2-, and 3-year cumulative incidence rates were 0.8%, 2.0%, and 2.8%, respectively.
An additional 28 patients had suspected ONJ as they met all the criteria with the exception of the 8-week duration. The cumulative incidence of both suspected and confirmed ONJ at 3 years was 3.7%.
The cumulative incidence rates of confirmed ONJ varied by primary tumor type, of whom breast cancer patients were the most commonly affected (32.1%), followed by prostate cancer (20.1%), lung cancer (19.1%), and multiple myeloma (16.6%) patients. The 3-year confirmed ONJ rates ranged from 2.4% in patients with breast cancer to 4.3% in those with multiple myeloma.
And the 3-year event rates of suspected and confirmed ONJ ranged from 2.9–5.3%, with the lowest and highest incidence again observed in patients with breast cancer and multiple myeloma, respectively.
Patients were 4.65 times more likely to develop ONJ if their treatment plan involved zoledronic acid dosing intervals of less than 5 weeks compared with patients who had a 5-week or longer dosing interval planned.
The actual number of zoledronic acid doses received was also significantly associated with ONJ, whereby patients who received more than the median number of doses within the first 1.0, 1.5, and 2.0 years were a respective 1.73, 2.72, and 3.60 times more likely to develop ONJ than those who received fewer doses. But the number of doses received within the first 6 months was not significantly associated with ONJ risk.
Additional ONJ risk factors included current smoking status (hazard ratio [HR]=2.12) and indicators of pre-existing dental disease. Specifically, individuals with more than 25 teeth at baseline were significantly less likely to develop ONJ than those with fewer teeth (HR=0.51), while those using removable or any type of dentures were significantly more likely to develop ONJ than patients with nonremovable or no dentures, respectively (HRs=2.02 and 1.83).
“Results were generally similar when both confirmed plus suspected ONJ cases were examined,” say Van Poznak and colleagues.
They admit that “[i]t is not yet known if an intervention made before initiating zoledronic acid treatment can modify these particular baseline risk factors for ONJ.”
Nevertheless, the researchers believe that “optimizing oral health and use of longer zoledronic acid intervals” could potentially modify ONJ risk.
And the team concludes: “Going forward, this well-annotated trial and its corresponding biorepository may yield clues to mechanisms underlying development of this challenging toxic effect, as well as additional biochemical, genomic, composite risk score, or other predictive factors associated with ONJ risk.”
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