Seoul St. Mary's Hospital: Denosumab beyond 1 year raises jaw necrosis risk in bone-metastatic prostate cancer

Prostate cancer patients with bone metastases who receive the bone-protective drug denosumab for more than a year face a significantly higher risk of jaw bone necrosis, according to new research.

A research team at the Catholic University of Korea College of Medicine said Tuesday it had published findings from an analysis of side effects and treatment outcomes based on denosumab administration duration in 3,307 patients with castration-resistant prostate cancer and bone metastases.

The research involved Choi Su-in, professor of clinical pharmacology at Seoul St. Mary's Hospital; Kim Seo-ri, professor of hematology-oncology at Bucheon St. Mary's Hospital; and Jeong Seung-pil, a researcher at the Catholic University of Korea PIPET Data Science Division.

Denosumab is a treatment that reduces skeletal complications — including fractures and spinal cord compression — in patients whose cancer has spread to the bones. It works by suppressing the activity of osteoclasts, the cells responsible for breaking down bone tissue.

However, prolonged use can inhibit the bone regeneration process, potentially causing necrosis of the jaw bone. Patients may also experience impaired healing of the jaw following dental procedures such as tooth extractions.

The research team analyzed national claims data from the Health Insurance Review and Assessment Service covering 2009 to 2024, dividing patients into three groups based on denosumab duration: six months or less, seven to 12 months, and 13 months or more. The average patient age was 72.6.

The three-year cumulative incidence of jaw necrosis was 3.3 percent among patients treated for seven to 12 months, but rose to 12.2 percent — roughly 3.7 times higher — among those treated for 13 months or more. That translates to approximately one in eight patients developing jaw necrosis when treatment extended beyond 13 months.

By contrast, the rate of skeletal complications such as fractures and spinal cord compression was about 4 percent in both groups. The findings suggest that extending denosumab treatment beyond one year does not provide additional protection against skeletal complications.

Total duration of treatment was more closely associated with the risk of side effects than the dosing interval. The disadvantage of long-term use was particularly pronounced in patients under 70, and those with a history of tooth extraction faced an even higher risk of jaw necrosis.

"We minimized this bias by virtually assigning all patients to three treatment strategies and comparing them as in a randomized clinical trial," Choi said. "We were able to present evidence from nationwide data showing that the balance of benefits and risks shifts at the one-year mark."

However, the researchers said the findings should not be interpreted as a call to discontinue denosumab unconditionally. Stopping the drug can trigger a rebound effect in which bone breakdown accelerates rapidly, they said, making careful, patient-specific judgment necessary.

"Jaw necrosis is a complication that significantly impairs eating and quality of life, and dental care is particularly important for patients with a history of tooth extraction," Kim said. "Dental and bone risks must be assessed together, and decisions on adjusting the dosing interval should be made carefully on a case-by-case basis."

The findings were published in the Oct. 21 issue of the international journal JAMA Network Open.

Meanwhile, Seoul St. Mary's Hospital said in August it had reached a cumulative total of 200 lutetium-177 prostate-specific membrane antigen (PSMA) nuclear medicine treatments for patients with metastatic prostate cancer — a milestone achieved across 84 patients since the hospital became the first in South Korea to introduce the treatment in November 2020.