Denosumab Duration Increases Jaw Necrosis Risk in Prostate Cancer

Men receiving oncological-dose denosumab for bone-metastatic castration-resistant prostate cancer face a distinct clinical trade-off after one year of treatment, as extended dosing substantially increases the incidence of osteonecrosis of the jaw without delivering additional skeletal protection, emjreviews.com reported.

South Korean Cohort Study Tracks 3,307 Patients

Researchers evaluated health insurance data from January 2009 to August 2024 in a nationwide retrospective cohort study published in JAMA Network Open. The analysis tracked 3,307 men who began denosumab therapy after developing bone metastases from castration-resistant prostate cancer. Participants had a mean age of 72.6 years, and the median follow-up period reached 42.6 months.

The overall three-year cumulative incidence of osteonecrosis of the jaw across the cohort stood at 9.8%. Patients treated for seven to 12 months faced a risk ratio of 2.22 compared to those receiving treatment for six months or less. Estimated three-year jaw complication rates rose from 1.47% in the six-month-or-less group to 3.28% for those treated up to a year.

Jaw Necrosis Rates Climb Beyond One Year

The risk of jaw complications escalated sharply among patients whose treatment extended past the 12-month mark. For men receiving denosumab for at least 13 months, the three-year cumulative incidence of osteonecrosis of the jaw reached 12.20%.

Comparing the group treated for 13 months or longer against patients receiving 7 to 12 months of therapy revealed an absolute risk difference of 8.93 percentage points. Despite the jump in adverse events, the extended treatment duration failed to produce a corresponding drop in bone-related complications.

Skeletal Event Reduction Plateaus at Twelve Months

The study tracked skeletal events—defined as pathological fractures, spinal cord compression, and bone surgery—which showed an overall three-year cumulative incidence of 4.9%. Treatment lasting 7 to 12 months reduced skeletal events compared to treatment lasting six months or less, with incidence rates of 3.82% versus 5.76% and a risk ratio of 0.66.

However, extending therapy beyond 13 months yielded no further decrease in skeletal events. The estimated incidence for the longer-duration group was 3.99%, resulting in an absolute risk difference of just 0.17 percentage points when compared directly against the 7-to-12-month treatment window.

Clinical Reassessment Recommendations

Study authors noted that the observational design means the findings do not establish a direct causal link between treatment duration and the observed outcomes. Because longer therapy increases jaw complications without providing extra skeletal benefit, the researchers support individualised reassessment of treatment duration after approximately one year.

The findings do not establish a universal stopping point for all patients. Clinical decisions require evaluating individual skeletal event risk, patient response to therapy, and potential adverse effects.