Impact of androgen suppression and zoledronic acid on bone mineral density and fractures in the Trans‐Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR) randomized controlled trial for locally advanced prostate cancer

Abstract

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.

Bone Health in Men with Prostate Cancer: Review Article

“…They found that compared with baseline DEXA measurements, BMD at the hip measured at 4 years was reduced with both 6 and 18 months of ADT (1.7% and 3.7%, respectively; p < 0.01) and this BMD reduction was prevented by concomitant administration of zoledronate. There was however, no significant difference in the primary endpoint of incidence of vertebral fractures seen although this was attributed to insufficient sample size and duration of follow-up [86]. Their results however confirmed those from several prior smaller studies [72][73][74]77] that all demonstrated a benefit with bisphosphonates in reducing BMD loss among prostate cancer patients on ADT.…”

The effect, moderators, and mediators of resistance and aerobic exercise on health‐related quality of life in older long‐term survivors of prostate cancer

“…Furthermore, men who were previously treated with bisphosphonates appeared to benefit more from the EX intervention than men who were not treated with bisphosphonates. Bisphosphonates are a class of drugs that prevent loss of bone mass, and in survivors of prostate cancer they may prevent ADT‐induced losses in bone mineral density . Differences in effects could not be explained by session attendance, but perhaps men who were treated with bisphosphonates were more able to comply with the prescribed exercise intensities and consequently had better HRQoL outcomes.…”

The best of both worlds — managing the cancer, saving the bone

“…Two randomized studies in patients with prostate cancer with no systemic metastases using zoledronic acid failed to show improvement of bone-metastases-free survival 128–130 . By contrast, patients with castrate-resistant prostate cancer who were given denosumab showed improvement of bone-metastasis-free survival from a median of 25.2 months on placebo to a median of 29.5 months on denosumab without any difference in overall survival 131 .…”