ONJ Rare After Dental Work While on Denosumab for Osteoporosis

Marlene Busko

February 26, 2019

Older women who received denosumab (Prolia, Amgen) for up to 10 years for osteoporosis had a low risk of osteonecrosis of the jaw (ONJ), although the risk was higher — albeit still quite small — if they had had major dental work, researchers report.

Rates of ONJ in patients with cancer receiving higher doses of denosumab are around 1% to 2% per year. ONJ is less common in patients with osteoporosis receiving lower doses of these medications, yet there is still concern among dentists and patients with osteoporosis, say lead author Nelson B. Watts, MD, from Mercy Health in Cincinnati, Ohio, and colleagues in their article published online February 13 in the Journal of Clinical Endocrinology & Metabolism.

"We found dental procedures were common among these patients, but ONJ was rare with only 5.2 cases for every 10,000 patient-years," Watts said in a press release issued by the Endocrine Society. 

Specifically, the rate of ONJ was 0.68% in women who had at least one invasive oral procedure/event — such as scaling or root planing (for periodontal disease), tooth extraction, dental implant, natural tooth loss, ill-fitting dentures, or root canal — versus 0.05% in the other women.

"Not only was ONJ rare," Watts added, "but the 11 cases [in more than 3500 women] where the outcome is known have healed."

"The ONJ cases typically followed dental extractions [especially multiple teeth] 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," he added.

Rate of ONJ With Denosumab "Reassuring", Similar to Bisphosphonates

These findings are from the 7-year FREEDOM Extension trial, which followed the 3-year Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) trial.

The new results "suggest that denosumab therapy may be continued during routine oral procedures and dental care and that the low risk of ONJ should be weighed against the previously demonstrated fracture prevention benefits of denosumab therapy in women with postmenopausal osteoporosis," Watts and colleagues conclude.

Invited to comment, American Society for Bone and Mineral Research (ASBMR) president Bart L. Clarke, MD, from the Mayo Clinic College of Medicine, Rochester, Minnesota, told Medscape Medical News that the rate of ONJ of 52 per 100,000 patients "is in the same ballpark as the bisphosphonates," which is "reassuring."

Guidelines recommend that patients have major dental work before they start taking antiresorptive therapy for osteoporosis, Clarke noted, and then pay close attention to their dental health while they are taking these drugs.

"This is, again, in an osteoporosis population, not a cancer population with higher doses [of denosumab]," he stressed, "so you have to keep in mind who you're treating and what the underlying risks [of ONJ] are."

Small Risk of Slow Healing, Exposed Jaw Bone After Dental Work

ONJ — defined as exposed bone in the jaw, usually after major dental work, that takes 8 weeks or more to heal — occurs in 1% to 2% of patients with cancer who receive high doses of zoledronic acid (4 mg intravenously [IV] monthly) or denosumab (120 mg subcutaneously [SC] every morning), Watts and colleagues write.

It is much less frequent (about 1 in 10,000 to 100,000 patients per year) in patients being treated for osteoporosis with lower doses of zoledronic acid (5 mg IV yearly) or denosumab (60 mg SC every 6 months) or oral bisphosphonates.

The current study aimed to provide an in-depth assessment of major dental work and ONJ cases in patients in the extension study.

In FREEDOM, women ages 60 to 90 years with osteoporosis were randomized to an SC injection of 60 mg of denosumab or placebo every 6 months for 3 years. In the FREEDOM Extension study, women in the placebo group were switched to denosumab (crossover group) and the other women continued on denosumab (long-term group).  

A total of 3591 women — 1731 women in the crossover group and 1860 women in the long-term group — were enrolled in the extension study and completed at least one survey about their recent major dental work or jaw surgery.

Overall, 45% of the women reported having at least one invasive dental procedure or jaw surgery, which ranged from scaling/root planing (29%) or tooth extraction (25%) to receiving a dental implant (5.9%), natural tooth loss (4%), or jaw surgery (0.9%). Procedure rates were similar in the two groups.

ONJ was positively adjudicated in 13 women — six in the crossover group and seven in the long-term denosumab group. Of these, one woman withdrew consent.

The women were 71 to 85 years old when they had ONJ, and it was not related to age. 

ONJ was treated with oral rinse, antibiotics, or surgery, and healed within 3.1 to 20.0 months, or 10 months on average.

Maintain Routine Dental Care

Based on their findings, Watts and colleagues recommend that "management of subjects with osteoporosis receiving denosumab should include routine dental care and treatment, including scaling/root planing when indicated, since nearly 30% of subjects reported receiving this procedure and none developed ONJ as a result."

It would be "prudent" to take extra care when performing multiple tooth extractions, and dental appliances should be made to fit well.

Moreover, "in general, there is little evidence to support that changes in normal dental procedures are necessary, and no data suggest that a 'drug holiday' or attempts to time certain [oral procedures and events] with denosumab would be beneficial in these subjects," he concluded.

The study was funded by Amgen. Watts has reported being a consultant and on the speakers' bureau for Amgen, among other companies. Complete disclosures for all authors are listed with the article. Clarke has reported serving on a data monitoring committee for Amgen and a scientific advisory board, and receiving research grants from Shire. He currently serves on a data monitoring committee for Bristol-Myers Squibb.

J Clin Endocrinol Metab. Published online February 13, 2019. Abstract

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