Denosumab (Prolia, Xgeva) treatment for postmenopausal women with osteoporosis may increase the risk of dental issues, researchers reported, though they were mostly minor.
According to 10-year data from the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial, nearly half of women on subcutaneous denosumab treatment reported at least one invasive oral procedure or event, said Nelson Watts, MD, of Mercy Health in Cincinnati, and colleagues.
These invasive dental events included getting dental implants, extraction of a tooth, jaw surgery, scaling or root planning, and natural tooth loss, the group explained in the Journal of Clinical Endocrinology & Metabolism.
On the other hand, the researchers found that osteonecrosis of the jaw (ONJ) was rather uncommon, at a rate of only 5.2 per 10,000 subject-years. Not surprising, however, occurrence of ONJ was higher in women with an invasive oral event than in those without (0.68% vs 0.05%).
"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," Watts explained in a press release. "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."
The analysis included women with osteoporosis who participated in the 3-year trial, who received 60 mg subcutaneous denosumab by injection every 6 months. This treatment was indicated for the prevention of new vertebral, nonvertebral, and hip fractures. Following the completion of this trial, the patients were invited to participate in the extension trial aimed at identifying dental risks, as the patients received 7 more years of denosumab.
History of invasive oral procedures was self-reported by the participants, while cases of ONJ were positively adjudicated and defined as exposed alveolar or palatal bone within the oral cavity where gingival or alveolar mucosa is typically located, which did not heal with treatment after 8 weeks.
About one third of the reported invasive dental events included tooth extraction, a dental implant, or natural tooth loss, with around 30% of events including scaling/root planning. Jaw surgery was rare in the cohort, occurring in only 33 participants (0.9%).
Overall, there were 13 women who had ONJ over the 7-year extension trial out of 1,621 participants -- 11 occurring in women with invasive oral events, one in a woman without such an event, and one case that was undefined.
This isn't the first time denosumab therapy has been tied to dental issues, however. According to the 2016 American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis, regular dental exams are recommended for these patients.
"An oral examination should be done in patients being considered for treatment with these agents; if significant dental issues are present, delaying the initiation of bisphosphonate or denosumab therapy until the dental issues have been corrected should be considered," the guidelines recommend.
They also recommend that "for patients already receiving bisphosphonates or denosumab who require invasive dental procedures, there is no evidence that discontinuing or interrupting treatment will change the outcome or reduce the risk of ONJ. Nonetheless, stopping treatment should at least be considered for patients undergoing extensive invasive dental procedures (e.g., extraction of several teeth)."
The study was funded by Amgen, the manufacturer of Prolia.
Watts reported relationships with AbbVie, Amgen, Radius, and Sanofi; other study authors also reported disclosures.
Denosumab and osteonecrosis of the jaw
Indication, denosumab and bisphosphonates are used to treat osteoporosis, Pagets disease, and as part of some cancer regimens, particularly for metastatic bone cancer and multiple myeloma. 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. The most common inciting event for ONJ appeared to be dental extractions, often of two or three teeth. Watts has received research support health Tip: Avoid Burns From Playground Equipment from Shire and has consulted for Abbvie, Amgen, and Radius. Conclusions: Denosumab combined with risk factors such as dental extraction, poor oral hygiene, use of removable apparatus, and chemotherapy may favor the development of ONJ. The next most common dental issue associated with ONJ seemed to be poorly-fitted dentures. Treatment for...
Content of ibandronic acid 2 mg, 4 mg, and 6 mg patient card. Other drug-specific risk factors for ONJ include drug potency (higher risk for highly potent compounds such as zoledronate, pamidronate and denosumab route of administration (higher risk for parenteral administration) and cumulative dose. In some cases dentists are telling my patients to either stop the drug that Im giving them or to wait to get the next dose, and theres absolutely nothing to support that. The finding comes from a new analysis of a 7-year extension study of denosumab use in 4,550 women health Tip: Care For a Wound At Home who participated in the 3-year, double-blind, phase 3 freedom trial (NCT00089791) that compared denosumab 60 mg and placebo every 6 months. Content of zoledronic acid 4 mg patient card.