Objective• To study the influence of adjuvant androgen suppression and bisphosphonates on incident vertebral and non-spinal fracture rates and bone mineral density (BMD) in men with locally advanced prostate cancer. Patients and Methods• Between 2003 and 2007, 1071 men with locally advanced prostate cancer were randomly allocated, using a 2 × 2 trial design, to 6 months i.m. leuprorelin (androgen suppression [AS]) before radiotherapy alone ± 12 months additional leuprorelin ± 18 months zoledronic acid (ZdA), commencing at randomization. • The main endpoint was incident thoraco-lumbar vertebral fractures, which were assessed radiographically at randomization and at 3 years, then reassessed by centralized review.• Subsidiary endpoints included incident non-spinal fractures, which were documented throughout follow-up, and BMD, which was measured in 222 subjects at baseline, 2 years and 4 years. Results• Incident vertebral fractures at 3 years were observed in 132 subjects. Their occurrence was not increased by 18 months' AS, nor reduced by ZdA.• Incident non-spinal fractures occurred in 72 subjects and were significantly related to AS duration but not to ZdA.• Osteopenia and osteoporosis prevalence rates at baseline were 23.4 and 1.4%, respectively, at the hip. • Treatment for 6 and 18 months with AS caused significant reductions in hip BMD at 2 and 4 years (P < 0.01) and ZdA prevented these losses at both time points. Conclusion• In an AS-naïve population, 18 months of ZdA treatment prevented the sustained BMD losses caused by 18 months of AS treatment; however, the study power was insufficient to show that AS duration or ZdA influenced vertebral fracture rates.

Objective: To determine if 6 months of neo-adjuvant androgen deprivation is associated with the long-term risk of cardiac mortality. Methods: In the TROG 96.01 trial, 802 men with locally advanced prostate cancer were randomized to radiotherapy either alone or with 3 or 6 months of neo-adjuvant androgen deprivation therapy (NADT). Competing risk methodology was used to derive the cumulative incidence of fatal cardiac events. Results: At 10 years, the cumulative incidence of fatal cardiac events for the radiation therapy alone arm was 7.54% compared to a nonstatistically significant decreased incidence of 6.44% in the 6-month NADT arm (p = 0.65). Men aged over 65 years were not at an increased risk. Additional androgen deprivation therapy given as secondary treatment at tumor progression did not confer an increased risk. Conclusion: These data suggest that fatal cardiac events are not more common in men receiving up to 6 months of NADT.

P1NP is not a sensitive serum marker of early BM in high-risk prostate cancer patients with BF and low prostate-specific antigen levels as its levels are affected by prior history of bone remodelling therapies such as ADT and bisphosphonates.