THE EFFECT OF COMBINED ANDROGEN BLOCKADE ON BONE TURNOVER AND BONE-MINERAL DENSITIES IN MEN TREATED FOR PROSTATE CARCINOMA - LONGITUDINAL EVALUATION AND RESPONSE TO INTERMITTENT CYCLIC ETIDRONATE THERAPY

BACKGROUND. Androgen receptor blocking agents have become an establish ed form of therapy for men with disseminated prostate carcinoma. The p urpose of this study was to evaluate markers of bone turnover and to m easure bone mineral densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy. METHODS. Twelve con secutive men with disseminated prostate carcinoma were evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin-rele asing hormone agonist (goserelin acetate) and an androgen antagonist ( flutamide). During the 6-12 month period, patients were treated with a djuvant intermittent cyclic etidronate therapy and calcium supplementa tion. Lumbar spine BMD was measured by spinal quantitative computed to mography (QCT) and femoral neck BMD by dual energy X-ray absorptiometr y (DXA). RESULTS. Combined androgen blockade resulted in all men achie ving serum free testosterone concentrations of <2.2 pmol/L (normal ran ge, 38-114 pmol/ L). The mean serum prostate specific antigen activiti es decreased from 130.8 +/- 46 to 6.9 +/- 4.4 ng/mL (P < 0.05). Althou gh serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measure ments remained unchanged, serum bone G1a-protein concentrations and ur inary deoxypyridinolene excretion rates increased significantly (P < 0 .01, respectively). Mean lumbar spine QCT decreased by 6.6 +/- 1.5% fr om 76.5 mg/cm(3) (95% confidence interval [95% CI], 57-96 mg/cm(3)) to 73.9 mg/cm(3) (95% CI, 55-93 mg/cm(3)) (P < 0.001) and mean femoral n eck DXA decreased by 6.5 +/- 1.3% from 0.94 g/cm(2) (95% CI, 0.81-1.07 g/cm(2)) to 0.91 g/cm(2) (95% CI, 0.79-1.04 g/cm(2)) (P < 0.001). Aft er treatment with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased by 7.8 +/- 3.7% to a final value of 75 mg/cm(3) ( 95% CI, 48.7-101 mg/cm(3)) (P = 0.001 compared with the initial 6 mont hs without intermittent cyclic etidronate therapy). Significant increa ses in BMD also were observed in the femoral neck and Ward's triangle. CONCLUSIONS. Androgen receptor blocking agents have an established ro le in the treatment of disseminated prostate carcinoma. However, combi ned androgen blockade in elderly men with disseminated prostate carcin oma results in high bone turnover with significant cancellous bone los s. The results of this study show that adjuvant therapy with intermitt ent cyclic etidronate may prevent these changes and decrease the risk of spinal fractures. Cancer 1998;83:1561-6. (C) 1998 American Cancer S ociety.