Incorporating Bone-Protecting Agents in Prostate Cancer Guidelines

Rahul Parikh, MD, a professor of medicine at the University of Kansas (KU) Medical Center, discussed the critical role of bone-protecting agents such as zoledronic acid and denosumab (Prolia, Xgeva) in patients with advanced prostate cancer, particularly in community practice settings. He emphasized that thoughtful workflow design and early intervention are essential to ensure compliance and reduce skeletal-related complications.

Parikh provided important clinical context by referencing data from prior phase 3 research, including studies evaluating abiraterone and prednisone in combination with radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC). In those trials, investigators observed an unexpectedly high rate of fractures among participants. Specifically, in the PEACE-3 trial (NCT02194842), after approximately 119 to 120 patients had been enrolled, a significant fracture risk was identified in both study arms. As a result, the protocol was amended to mandate the use of bone-protective therapy—either zoledronic acid or denosumab—for all patients to mitigate this risk.

In clinical practice, Dr. Parikh explained, providers often rely on tools such as the FRAX score or baseline bone mineral density assessment with a DEXA scan to determine which patients are at greatest risk for osteopenia or osteoporosis. These assessments help stratify fracture risk and guide decisions regarding initiation of bone-targeted therapy. However, more recent trial data and evolving guidelines have increasingly supported broader and earlier implementation of these agents, particularly for patients receiving long-term androgen deprivation therapy (ADT).

He underscored that ADT, which continues through both hormone-sensitive and castration-resistant phases of disease, can significantly weaken bone density over time. Therefore, screening and intervention should ideally begin at the initiation of hormonal therapy rather than waiting until patients progress to castration-resistant disease. By integrating fracture risk assessment into the initial visit and proactively prescribing bone-protecting agents when appropriate, clinicians can reduce skeletal complications and improve long-term outcomes for patients with advanced prostate cancer.