Risedronate recovers bone loss in patients with prostate cancer undergoing androgen-deprivation therapy.

OBJECTIVES: To perform a prospective observational study between risedronate and no risedronate (control) groups to determine the effectiveness of risedronate against bone loss in patients with prostate cancer (PCa) receiving androgen-deprivation therapy (ADT). ADT for PCa has iatrogenic complications (eg, bone loss and fracture). METHODS: We enrolled 60 Japanese patients with PCa who were receiving ADT or were newly scheduled for ADT. The lumbar spine bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry. Patients with a BMD <90% of the young adult mean received risedronate. We analyzed 29 and 27 patients in the risedronate and control groups, respectively. The BMD, urinary deoxypyridinoline, and serum bone alkaline phosphatase were measured as bone turnover markers at 6 and 12 months. RESULTS: The BMD/young adult mean ratio correlated inversely with the duration of ADT. The initial mean BMD was significantly lower in the risedronate group than in the control group (1.02 +/- 0.19 vs 1.19 +/- 0.16 g/cm(2)). We focused on patients treated with ADT for >6 months. The mean percentage of changes in the BMD/young adult mean ratio of the risedronate and control groups was +2.6 +/- 4.5% and -2.8 +/- 2.6% after 1 year, respectively (P = .0001). The urinary deoxypyridinoline and bone alkaline phosphatase in the risedronate group decreased significantly after 12 months compared with the levels in the controls. CONCLUSIONS: The results of our study have shown that oral administration of risedronate is effective for the recovery of ADT-induced bone loss in patients with PCa.

Androgen-independent growth in LNCaP cell lines and steroid uridine diphosphate-glucuronosyltransferase expression.

AIM: To investigate the mechanism of androgen-independent growth of prostate cancer after androgen ablation in LNCaP cells and the effect of glucuronidation activity. METHODS: To establish androgen-independent growth in prostate cancer LNCaP-SF, continuous passage was performed in androgen-stripped medium and the cells were evaluated for glucuronidation activity. The expression vector of antisense uridine diphosphate glucuronosyl-transferase (UGT) 2B15 cDNA was also constructed and evaluated. RESULTS: LNCaP-SF lead to a higher expression in UGT2B15 and their glucuronidation activity is 2.5 times higher than that of LNCaP cells. Significantly fewer LNCaP and LNCaP-SF than control were transfected with the antisense UGT2B15 cDNA, suggesting that UGT2B15 plays an important part in the glucuronidation activity of androgens in both cells. CONCLUSION: The alteration of UGT2B15 expression in LNCaP-SF cells is proposed as a biological characteristic involved in the growth of hormone-refractory prostate cancer.