Risk for osteonecrosis of the jaw higher with denosumab vs. bisphosphonates
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Adults with osteoporosis have a higher risk for developing osteonecrosis of the jaw with denosumab therapy compared with bisphosphonates, according to study findings published in the Journal of Bone and Mineral Research.
“Although we observed an increasing number of osteonecrosis of the jaw cases in our daily practice during the past years, we were surprised that the incidence rate and risk of osteonecrosis of the jaw under denosumab was higher compared with bisphosphonates,” Judith Everts-Graber, MD, senior rheumatologist at OsteoRheuma Bern AG in Bern, Switzerland, told Healio. “This is a new finding, at least in patients with osteoporosis. It has already been demonstrated in some studies who analyzed the risk of osteonecrosis of the jaw in patients with cancer, where higher dosages of antiresorptive drugs are used at frequent intervals.”
Everts-Graber and colleagues reviewed data from 9,956 adults with suspected osteoporosis who underwent at least one DXA scan and had data available in the Swiss Society of Rheumatology national register. Participants were followed from January 2015 to September 2019. Demographics, data on risk factors for osteoporotic fractures, T-scores, trabecular bone scores, clinical and morphometric fracture data, and anti-osteoporotic therapies were collected. Medical records were reviewed for mentions of osteonecrosis of the jaw or dental procedures with complications. Potential cases of osteonecrosis of the jaw were reviewed by two maxillofacial surgeons based on health reports from dentists and surgeons, along with radiographs and histological results.
A total of 3,068 adults in the cohort received bisphosphonates, denosumab (Prolia, Amgen) or both sequentially. There were 17 diagnoses of osteonecrosis of the jaw, with 12 coming in people receiving denosumab and five in patients on bisphosphonate therapy. The osteonecrosis of the jaw incidence rate was 4.5 per 10,000 patient-years for bisphosphonate therapy and 28.3 per 10,000 patient-years for denosumab therapy. More than half of the adults with osteonecrosis of the jaw had relevant risk factors such as smoking, glucocorticoid therapy and type 2 diabetes, rheumatoid arthritis and two were receiving aromatase inhibitors for breast cancer treatment.
Adults on denosumab therapy had a higher risk for osteonecrosis of the jaw compared with bisphosphonate therapy (HR = 3.49; 95% CI, 1.16-10.5; P = .026). Risks were similar in sensitivity analysis excluding any treatments taking place prior to the approval of denosumab in Switzerland.
“Patients and physicians should be aware of osteonecrosis of the jaw as a possible adverse effect,” Everts-Graber said. “Primary prevention is recommended to restore and maintain good oral health in patients taking bisphosphonates or denosumab. Other risk factors for osteonecrosis of the jaw should be minimized — quitting smoking, reduction of glucocorticoids, replacement of poorly fitting dentures. If an invasive oral procedure is necessary during treatment, the dentists should know about the anti-osteoporotic therapy so that they can apply preventive measures.”
Of the 12 adults with osteonecrosis of the jaw on denosumab, nine had previously been treated with bisphosphonates, with an intermediate drug holiday between 4 months and 6 years. The five adults who were on bisphosphonates at the time of their osteonecrosis of the jaw diagnosis did not have prior denosumab therapy.
Everts-Graber said the pathogenesis of denosumab-related osteonecrosis of the jaw and the toxic effects of sequential therapy with bisphosphonates and denosumab need to be studied in the future. She added that preventive strategies to minimize osteonecrosis of the jaw risk for those on antiresorptive therapy should also be created.
For more information:
Judith Everts-Graber, MD, can be reached at judith.everts@hin.ch.
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Nelson Watts, MD, FACP, MACE, CCD
Everts-Graber and colleagues report a higher rate of osteonecrosis of the jaw in osteoporosis patients “under treatment” with denosumab (12 of 4,326, or 28.3 cases per 10,000 person-years) compared with patients “under treatment” with bisphosphonates (5 of 11,101, or 4.5 per 10,000 person-years). This is technically correct, but partially conceals the fact — clearly stated in their paper — that 9 of the 12 cases in patients “under treatment” with denosumab had prior treatment with bisphosphonates, mean 6.7 years. Their conclusion that changing from bisphosphonate treatment to denosumab may be a risk factor for osteonecrosis of the jaw is likely correct, but the title that implies that denosumab treatment is more likely to lead to osteonecrosis of the jaw is misleading. Even at a rate of 28.3 per 10,000 person-years, the risk of osteonecrosis of the jaw is low.
I believe that the term “osteonecrosis” is incorrect. If the bone gets infected, it is osteomyelitis and necrotic. Nuclear medicine scans of exposed bone in non-infected patients with “osteonecrosis of the jaw” show increased uptake. “Necrosis” implies “dead bone,” which should not be taking up radioisotope.
Missing from the study is the frequency of dental extractions or other invasive procedures between their groups — possibly more frequent in patients “under treatment” with denosumab. It would be desirable to know if there were differences in presentation of osteonecrosis of the jaw between their groups, if they were treated successfully and if there were differences in healing times.
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