DENOSUMAB treatment duration was associated with a trade-off between osteonecrosis of the jaw (ONJ) and skeletal event risk in men with bone-metastatic castration-resistant prostate cancer, with treatment beyond 12 months linked to substantially higher jaw complications but no additional reduction in skeletal events.
Researchers conducted a nationwide retrospective cohort study using South Korean health insurance data from January 2009 to August 2024. The analysis included 3,307 men with bone-metastatic castration-resistant prostate cancer who initiated oncological-dose denosumab. Participants had a mean age of 72.6 years, and median follow-up was 42.6 months.
The overall three-year cumulative incidence of ONJ was 9.8% (95% confidence interval [CI]: 8.7–11.0%). Compared with treatment lasting six months or less, treatment for 7–12 months was associated with a higher risk of ONJ (risk ratio [RR]: 2.22; 95% CI: 1.21–4.11). The estimated three-year incidence was 3.28% with 7–12 months of treatment, compared with 1.47% with six months or less.
The risk increased further with treatment lasting at least 13 months, reaching 12.20% (95% CI: 10.86–13.68%). Compared with the 7–12-month group, this represented an absolute risk difference of 8.93 percentage points (95% CI: 7.16–10.64).
The overall three-year cumulative incidence of skeletal events was 4.9% (95% CI: 4.2–5.7%). These events included pathological fracture, spinal cord compression, and surgery to bone.
Treatment for 7–12 months was associated with a lower risk of skeletal events than treatment for six months or less: 3.82% versus 5.76% (RR: 0.66; 95% CI: 0.45–0.97). However, extending treatment to at least 13 months was not associated with a further reduction. The estimated incidence was 3.99%, with an absolute risk difference of 0.17 percentage points compared with 7–12 months (95% CI: −1.03 to 1.31).
The researchers used statistical methods to compare treatment durations while accounting for differences in patient follow-up. The study was observational, however, and the associations do not establish that treatment duration directly caused the differences in outcomes.
The findings suggest that denosumab treatment for 7–12 months may be associated with a balance between skeletal protection and ONJ risk, while longer treatment may increase jaw complications without providing additional skeletal benefit. The authors therefore support individualised reassessment of treatment duration after approximately one year.
The results should not be interpreted as establishing a universal stopping point. Decisions about continuing denosumab require consideration of each patient’s skeletal event risk, treatment response, and potential adverse effects.
Reference
Kim S et al. Denosumab therapy duration and osteonecrosis of the jaw and skeletal events in bone-metastatic prostate cancer. JAMA Netw Open. 2026;9;(10):e2639765.
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