Androgen deprivation therapy (ADT) is a cornerstone of prostate cancer management but is well known to adversely affect bone health. In recent years, the addition of androgen receptor pathway inhibitors (ARPIs) to ADT—referred to as maximal androgen blockade (MAB)—has become standard of care across multiple disease settings due to demonstrated survival benefits. However, whether intensifying hormonal therapy further increases fracture risk has remained unclear.
To address this concern, the researchers performed a systematic literature review and meta-analysis comparing fracture incidence in patients treated with MAB versus ADT alone. Clinical trials were identified through searches of the PubMed/Medline and Cochrane Library databases. Eligible studies included men with prostate cancer receiving ADT either alone or in combination with an ARPI. The investigators calculated pooled odds ratios for fracture risk using random-effects models and also assessed reported use of bone-protecting agents (BPAs).
The review led to the following findings:
- The meta-analysis included 17 studies comprising a total of 16,162 patients with prostate cancer.
- Among these, 9,240 patients were treated with maximal androgen blockade, while 6,922 received androgen deprivation therapy alone.
- Patients receiving maximal androgen blockade showed a consistently higher risk of bone fractures compared with those on ADT monotherapy.
- Across all androgen receptor pathway inhibitor classes, MAB was associated with a statistically significant increase in fracture risk, with pooled odds ratios ranging from 1.5 to 2.4.
- The magnitude of fracture risk did not differ meaningfully among the different ARPIs evaluated.
- The findings suggest that the increased fracture risk is a class effect related to intensified androgen suppression rather than to any specific ARPI.
- Use of bone-protecting agents was inadequately reported, with only seven studies providing relevant data.
- Limited reporting on bone-protecting agents prevented a clear assessment of their role in reducing fracture risk among patients receiving MAB.
The authors emphasized that their findings have important clinical implications, particularly as long-term MAB is increasingly used in both hormone-sensitive and castration-resistant prostate cancer. Given the clear association between MAB and fracture risk, proactive bone health management should be considered an essential component of care.
The researchers concluded that maximal androgen blockade significantly increases the risk of fractures compared with ADT alone, regardless of the ARPI used. They recommend routine consideration of bone-protecting agents for patients receiving prolonged MAB, with dosing and treatment schedules tailored to the specific prostate cancer setting and individual patient risk profile.
Overall, the study highlights the need to balance survival benefits with long-term skeletal safety when intensifying hormonal therapy in prostate cancer.
Reference:
Saporita, I., Calabrese, M., Carfi, F. M., Mogavero, A., Puglisi, M., Treglia, G., Vogl, U. M., Gillessen, S., Pereira Mestre, R., Pedrani, M., Pecoraro, G., Salfi, G., Erhart, C. C., Lin, H. M., Tortola, L., Di Maio, M., Tucci, M., Buttigliero, C., & Turco, F. (2026). Risk of bone fractures in patients with prostate cancer treated with maximal androgen blockade therapy: A systematic literature review and meta-analysis. Prostate Cancer and Prostatic Diseases, 1-9. https://doi.org/10.1038/s41391-026-01077-9
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