The anti osteo porotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade - A double blind, randomized, placebo-controlled crossover study

BACKGROUND. Prostate carcinoma therapy with combined androgen blockade may result in high bone-turnover with significant bone loss. This study was und ertaken to evaluate the antiosteoporotic efficacy of intravenous pamidronat e in a double blind, randomized, placebo-controlled, crossover study. METHODS. Twenty-one consecutive men with metastatic prostate carcinoma who were receiving combined androgen blockade with a long-acting gonadotropin-r eleasing hormone agonist (gosarelin acetate) and an androgen antagonist (fl utamide or bicalutamide) were evaluated at baseline and at 6 and 12 months after therapy. They were randomly assigned to receive a single intravenous infusion of 500 niL of normal saline solution diluted with either pamidrona te (90 mg) or placebo at baseline and with a crossover at 6 months. Lumbar- spine bone-mineral densities (BMDs) were measured by spinal quantitative co mputed tomography (QCT), femoral neck BMDs were measured by dual-energy X-r ay absorptiometry (DXA), and markers of bone turnover were measured by noni nvasive methods. Data on 10 men with localized prostate carcinoma who were treated with radiotherapy alone, over the same period, was collected for co mparison studies. RESULTS, The mean age of the men was 75.1 years +/- 1.6 years. One man with drew from the study because of deteriorating health, and two died from meta static disease within the first 6 months. Combined androgen blockade normal ized serum prostate-specific antigen activities (from an initial mean value of 86.2 ng/mL +/- 10.1 ng/mL) and maintained serum free testosterone conce ntrations in the hypogonadal range (< 2.2 pmol/L) in all men throughout the study. Treatment with pamidronate resulted in a 7.8% +/- 1.5% increase in mean lumbar spine QCT from 79.4 mg/cm(3) (95% confidence interval [CI], 64- 94 mg/cm(3)) to 85.6 mg/cm(3) (95% CI, 70-101 mg/cm(3)) (P = 0.0005) and a 2% +/- 0.9% increase in mean total femoral neck DXA from 0.98 g/cm(2) (95% Cl, 0.90 -1.05 g/cm(2)) to 1.0 mg/cm(2) (95% Cl, 0.91-1.08 g/cm(2)) (P = 0. 02). Conversely, treatment with placebo, resulted in a 5.7% +/- 1.6% decrea se in mean lumbar spine QCT and a 2.3% +/- 0.7% decrease in mean total femo ral neck DXA (P = 0.0001 and P = 0.0007 for the comparison of percentage ch ange between the pamidronate and placebo treatments). After pamidronate the rapy, serum bone Gla-protein concentrations decreased by 16.8% +/- 5.9%, an d urinary deoxypyridinoline excretion rates decreased by 18.5% +/- 12.8% (P < 0.01 respectively for the comparison between pamidronate and placebo tre atment). CONCLUSIONS, This study demonstrated that a single intravenous infusion of pamidronate (90 mg) significantly reduced the high bone turnover and bone l oss (for at least 6 mos) in men with prostate carcinoma who had been render ed hypogonadal with combined androgen blockade therapy. (C) 2001 American C ancer Society.