A Phase 3, Double-blind, Randomised, Parallel-group, Placebo-controlled Study of Oral Weekly Alendronate for the Prevention of Androgen Deprivation Bone Loss in Nonmetastatic Prostate Cancer: The Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) Study

Background: Androgen-deprivation therapy (ADT) induces loss of bone mineral density (BMD) and increases the risk of fractures in patients with prostate cancer (PCa). We sought to determine whether a weekly dose of alendronate, an oral bisphosphonate, could reduce this unwanted side-effect. Objective: To assess whether once-weekly oral alendronate therapy would maintain or improve BMD in men initiating ADT for localised PCa. Design, setting, and participants: A multicentre, double-blind, randomised, placebo-controlled study, we included hormonally naive PCa patients initiating ADT with leuprolide acetate 30 mg intramuscularly every 4 mo. Intervention: Patients were randomised to receive either oral alendronate 70 mg once weekly or placebo for 1 yr. Both groups received daily calcium 1 g and vitamin D 400 international units. Outcome measurements and statistical analysis: Changes in BMD (at the lumbar spine [LS] and total hip [TH]) and bone markers. Results and limitations: One hundred ninety-one subjects were enrolled, and 186 were randomised between alendronate (n = 84) and placebo (n = 102). The alendronate group demonstrated a mean spine BMD increase of 1.7% compared with -1.9% in the placebo group (p < 0.0001). Alendronate also increased the BMD at the hip (percent change: 0.7%) compared to placebo (-1.6%). Median urinary N-terminal crosslinking telopeptide of type I collagen (Ntx) values decreased by 3.5% in the alendronate group and increased by 16.5% in the placebo arm, even after adjusting for centre (p = 0.510) and baseline urinary Ntx (p < 0.0001). Bone-specific alkaline phosphatase (BSAP) decreased a median of 2.25% in the alendronate group and increased a median of 3.12% in the placebo arm, regardless of centre or baseline BSAP or other covariates (p < 0.0001). The safety and tolerability profile was similar for the two treatment groups. Conclusions: Although the study was closed early because of slow accrual, it showed that weekly oral alendronate prevented bone loss and increased bone mass in addition to decreasing bone turnover in patients initiating ADT for localised PCa, with few related side-effects. (C) 2012 Published by Elsevier B.V. on behalf of European Association of Urology.