Longer Denosumab Use in Bone-Metastatic Prostate Cancer Tied to More ONJ

In men with bone-metastatic castration-resistant prostate cancer (CRPC), denosumab treatment beyond 12 months was associated with a markedly higher risk of osteonecrosis of the jaw (ONJ) without a further reduction in skeletal events, according to a nationwide cohort study published in JAMA Network Open.

The investigators noted that denosumab reduces skeletal-related events in bone-metastatic prostate cancer but carries a cumulative risk of ONJ. The treatment duration that best balances these risks has not been established in clinical settings. The retrospective study used Korean Health Insurance Review and Assessment Service claims from January 2009 through August 2024 to emulate a target trial; patients were not randomized.

The analysis included 3307 men (mean age, 72.6 years) who initiated oncologic-dose (120mg) denosumab (Xgeva, Amgen). Using a clone-censor-weight approach with death as a competing event, investigators estimated 3-year cumulative incidence for treatment durations of 6 months or less, 7 to 12 months, and 13 months or longer.

Compared with 6 months or less, 7 to 12 months of treatment was associated with a lower risk of skeletal events (3.82% vs 5.76%; risk ratio, 0.66; 95% CI, 0.45-0.97). Skeletal events were defined as pathologic fracture, spinal cord compression, or surgery to bone. The same comparison showed a higher risk of ONJ (3.28% vs 1.47%). With 13 months or longer, ONJ incidence reached 12.20%, 8.93 percentage points higher than with 7 to 12 months, while skeletal event risk was similar (3.99%; risk difference, 0.17 percentage points; 95% CI, −1.03 to 1.31).

Prior tooth extraction was the only baseline risk factor for ONJ. Among patients younger than 70 years, treatment beyond 12 months was unfavorable across all benefit-harm weightings examined. When radiotherapy was added to the skeletal composite, the pattern attenuated to similar risks across strategies.

The authors cited several limitations. Clinical details such as cancer stage and performance status were unavailable, leaving residual confounding possible. Outcomes were identified from codes, and the ONJ code had a positive predictive value of 71.6% in a validation cohort. The data came from a single country with high dental care access. The authors concluded that the findings support individualized reassessment of denosumab after approximately 1 year rather than routine indefinite continuation, noting that reassessment is not a recommendation to stop.

Source: Kim S, Jung S, Bu 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. doi:10.1001/jamanetworkopen.2026.39765