Despite the relatively high prevalence of self-reported invasive oral procedures and events in women treated with denosumab and its subsequent effect on increasing the risk for osteonecrosis of the jaw, rates of osteonecrosis of the jaw remain low and tend to resolve with further therapy. This is according to study results published in The Journal of Clinical Endocrinology & Metabolism.
Data from the double-blind, placebo-controlled FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study were used for analysis. The study cohort included postmenopausal women ages 60 to 90 years who had lumbar spine or total hip bone mineral density T-score less than -2.5 at either site and a history of ≤2 moderate vertebral fractures.
The 3-year FREEDOM trial was followed by the FREEDOM Extension portion, a 7-year period of open-label denosumab treatment. Investigators assessed participants’ self-reported history of invasive oral procedures and events at the start of Extension to 2.5 years, as well as oral events in the preceding 6 months. Questionnaires were administered every 6 months until the end of the extension trial.
A total of 4550 participants were enrolled in the extension study and 78.9% (n = 3591) of these patients participated in and completed the oral events survey. Approximately 45% of participants reported having ≥1 oral procedure or event during the follow-up period. Those in the long-term denosumab group received denosumab for the duration of the FREEDOM study as well as during the extension, and the “crossover” group received placebo during the FREEDOM study and denosumab during the extension study. Data from the 2 groups revealed similar rates of specific oral procedures and events, including scaling/root planing (28.5% vs 29.1%, respectively), tooth extraction (24.6% vs 25.1%, respectively), dental implants (6.0% vs 5.8%, respectively), natural tooth loss (4.0% vs 4.2%, respectively), and jaw surgery (0.9% vs 0.9%, respectively).
In the FREEDOM Extension phase, the exposure-adjusted rate of osteonecrosis of the jaw was 5.2/10,000 subject-years. The incidence of osteonecrosis of the jaw was greater in participants who reported an oral procedure or event (0.68%) vs participants who did not report an invasive oral event (0.05%). Of 12 cases of self-reported osteonecrosis of the jaw, 10 resolved with treatment, 1 person was undergoing treatment at study end but appeared to be healing, and the outcome of the final case was unknown because of withdrawal of consent.
Limitations to the study included the self-reported nature of oral procedures as well as the potentially underestimated number of invasive oral events in the final cohort.
According to the investigators, the findings “suggest that denosumab therapy may be continued during routine oral procedures and dental care, and that the low risk [for osteonecrosis of the jaw] should be weighed against the previously demonstrated fracture prevention benefits of denosumab therapy in women with postmenopausal osteoporosis.”
This study was funded by Amgen Inc, which manufactures denosumab, and multiple authors declared associations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Watts NB, Grbic JT, Binkley N, et al. Invasive oral procedures and events in women with postmenopausal osteoporosis treated with denosumab for up to 10 years [published online February 13, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01965