Study finds oral side effects are uncommon and manageable
Oral complications are rare in women taking medications for postmenopausal osteoporosis, according to a study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.
An oral complication called osteonecrosis of the jaw (ONJ) is exposed bone in the jaw that is slow to heal (8 weeks or longer, with effective treatment), usually after a major dental procedure. It was first reported in 2003 in patients with advanced cancer receiving high doses of zoledronic acid and denosumab (medications also used to treat osteoporosis). Rates in cancer patients receiving high doses are around 1 percent to 2 percent per year. ONJ is less common in patients with osteoporosis receiving lower doses of these medications (about one case every 10,000 patient-years), yet there is still a lot of concern among dentists and patients.
"Our study covered the seven-year extension of the denosumab pivotal trial. We found dental procedures were common among these patients, but ONJ was rare with only 5.2 cases for every 10,000 patient-years. Not only was ONJ rare, but the 11 cases where the outcome is known have healed," said the study's lead author, Nelson Watts, M.D., of Mercy Health in Cincinnati, Ohio. "The ONJ cases typically followed dental extractions or poorly fitting dentures. Of the 212 patients with dental implants, only one developed ONJ, and she continued denosumab, healed her ONJ, and still has the implant."
Researchers used data from the seven-year FREEDOM Extension trial to assess information on oral procedures and cases of ONJ in women taking denosumab for postmenopausal osteoporosis. They found 45 percent of patients had at least one invasive dental procedure, but the overall rate of ONJ was low. ONJ incidence was higher in those reporting a dental procedure.
"My hope is our study will help patients and oral care providers be better informed about the low risk of ONJ compared to the fracture prevention benefits of antiresorptive therapy in women with postmenopausal osteoporosis," Watts said.
Antiresorptive therapy has been associated with osteonecrosis of the jaw (ONJ), an infrequent but potentially serious adverse event.
To assess information on invasive oral procedures and events (OPEs) - dental implants, tooth extraction, natural tooth loss, scaling/root planing, jaw surgery - during the 7-year FREEDOM Extension and to present details of positively adjudicated ONJ cases.
Randomized, double-blind, placebo-controlled 3-year trial (FREEDOM) followed by 7 years of open-label denosumab (FREEDOM Extension). At Extension Year 3, women were asked to record their history of invasive OPEs since the start of the Extension to Year 2.5 and oral events in the prior 6 months. The questionnaire was then administered every 6 months (Q6M) until the end of the Extension.
Multicenter, multinational clinical trial.
Women with postmenopausal osteoporosis.
Subcutaneous denosumab 60mg or placebo Q6M for 3-years, then 7 years of open-label denosumab.
Main outcome measures:
Self-reports of OPEs and adjudicated cases of ONJ.
45.1% of respondents reported at least one invasive OPE. The exposure-adjusted ONJ rate in FREEDOM Extension was 5.2 per 10,000 subject-years. ONJ incidence was higher in those reporting an OPE (0.68%) than not (0.05%).
While invasive OPEs were common in these denosumab-treated women and were associated with an increased ONJ incidence, the overall rate of ONJ was low, and all cases with complete follow-up resolved with treatment.
Watts NB, Grbic JT, Binkley N, Papapoulos S, Butler PW, Yin X, Tierney A, Wagman RB, McClung M. Invasive Oral Procedures and Events in Women With Postmenopausal Osteoporosis Treated With Denosumab for up to 10 Years. J Clin Endocrinol Metab. 2019 Feb 13. doi: 10.1210/jc.2018-01965. [Epub ahead of print]