DENVER – Osteonecrosis of the jaw (ONJ) was a rare adverse event in women taking denosumab for postmenopausal osteoporosis, with a 0.7% rate for women who reported an invasive oral procedure or event while taking the drug and a 0.05% rate for women who did not have such procedures, Nelson Watts, MD, reported at the annual meeting of the American Society of Bone and Mineral Research.
The finding comes from a new analysis of a 7-year extension study of denosumab use in 4,550 women who participated in the 3-year, double-blind, phase 3 FREEDOM trial (NCT00089791) that compared denosumab 60 mg and placebo every 6 months. Those who missed 1 dose or fewer and completed visits through year 3 of the initial study were eligible to continue in the 7-year, open-label extension study. Those who had received placebo in the initial trial were crossed over to denosumab for the extension study.
Extension study participants were instructed to chronicle invasive oral procedures and events that had occurred in the initial trial and completed an oral event questionnaire once every 6 months of the extension trial.
All surveys were completed by 3,591 (79%) of the extension study participants, and 45.1% reported at least one invasive oral procedure or event during that time. The frequency of events was similar for the crossover and long-term denosumab groups; these events included scaling or root planing (29.1% and 28.5%), tooth extraction (25.1% and 24.6%), dental implant (5.8% and 6.0%), natural tooth loss (4.2% and 4.0%), and jaw surgery (0.9% and 0.9%). ONJ occurred at a rate of 5.2 cases per 10,000 patient-years of denosumab use, said Nelson Watts, MD, director of osteoporosis and bone health services at Mercy Health Services in Cincinnati, Ohio.
Of the 12 ONJ cases identified in the study, 11 occurred in women who reported an invasive oral procedure or event. This translated to a 0.7% risk of ONJ in women who reported an invasive oral procedure or event (11 in 1,621) and a 0.05% risk in women who did not (1 in 1,970).
The most common inciting event for ONJ appeared to be dental extractions, often of two or three teeth. The next most common dental issue associated with ONJ seemed to be poorly-fitted dentures.
ONJ resolved with treatment in 10 of 12 cases; one case was ongoing at the end of the study and one had an unknown outcome because the subject had withdrawn from the study. “With effective dental therapy, healing is the most likely outcome,” said Dr. Watts.
In clinical trials, ONJ occurred at a rate between 1 and 10 per 10,000 patient-years. A report in 2003, however, described severe ONJ in 36 cancer patients who received bisphosphonates (https://www.ncbi.nlm.nih.gov/pubmed/12966493).
The denosumab doses that cancer patients receive can be 10 to 12 times higher than the typical dose given to a postmenopausal woman being treated for osteoporosis.
“I can’t tell you how many phone calls I get from patients who are worried somehow or worried in situations created by their dentists that whatever procedure they’re going to have is going to end horribly,” Dr. Watts said. “In some cases dentists are telling my patients to either stop the drug that I’m giving them or to wait to get the next dose, and there’s absolutely nothing to support that.”
The study was funded by Amgen, the maker of denosumab (Prolia). Dr. Watts has received research support from Shire and has consulted for Abbvie, Amgen, and Radius. He is on the speakers’ bureau for Amgen, Radius, and Shire.