Diamond T, Campbell J, Bryant C, Lynch W
Metabolic Bone Unit, St. George Hospital, Kogarah, Sydney, Australia.
Cancer. 1998 Oct 15;83(8):1561-6.
Androgen receptor blocking agents have become an established form of therapy for men with disseminated prostate carcinoma. The purpose of this study was to evaluate markers of bone turnover and to measure 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.
Twelve consecutive men with disseminated prostate carcinoma were evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin-releasing hormone agonist (goserelin acetate) and an androgen antagonist (flutamide). During the 6-12 month period, patients were treated with adjuvant intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine BMD was measured by spinal quantitative computed tomography (QCT) and femoral neck BMD by dual energy X-ray absorptiometry (DXA).
Combined androgen blockade resulted in all men achieving serum free testosterone concentrations of <2.2 pmol/L (normal range, 38-114 pmol/ L). The mean serum prostate specific antigen activities decreased from 130.8+/-46 to 6.9+/-4.4 ng/mL (P < 0.05). Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements remained unchanged, serum bone Gla-protein concentrations and urinary deoxypyridinolene excretion rates increased significantly (P < 0.01, respectively). Mean lumbar spine QCT decreased by 6.6+/-1.5% from 76.5 mg/cm3 (95% confidence interval [95% CI, 57-96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55-93 mg/cm3) (P < 0.001) and mean femoral neck DXA decreased by 6.5+/-1.3% from 0.94 g/cm2 (95% CI, 0.81-1.07 g/cm2) to 0.91 g/cm2 (95% CI, 0.79-1.04 g/cm2) (P < 0.001). After treatment with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased by 7.8+/-3.7% to a final value of 75 mg/cm3 (95% CI, 48.7-101 mg/cm3) (P=0.001 compared with the initial 6 months without intermittent cyclic etidronate therapy). Significant increases in BMD also were observed in the femoral neck and Ward's triangle.
Androgen receptor blocking agents have an established role in the treatment of disseminated prostate carcinoma. However, combined androgen blockade in elderly men with disseminated prostate carcinoma results in high bone turnover with significant cancellous bone loss. The results of this study show that adjuvant therapy with intermittent cyclic etidronate may prevent these changes and decrease the risk of spinal fractures.
雄激素受体阻断剂已成为治疗播散性前列腺癌男性患者的一种既定治疗方式。本研究的目的是评估骨转换标志物，并测量接受间歇性环磷酰胺治疗6个月前后联合雄激素阻断治疗的播散性前列腺癌男性患者的骨矿物质密度（BMD）。
连续12例播散性前列腺癌男性患者在接受长效促性腺激素释放激素激动剂（醋酸戈舍瑞林）和雄激素拮抗剂（氟他胺）治疗后的0、6和12个月进行评估。在6 - 12个月期间，患者接受辅助间歇性环磷酰胺治疗和补钙。腰椎BMD通过脊柱定量计算机断层扫描（QCT）测量，股骨颈BMD通过双能X线吸收法（DXA）测量。
联合雄激素阻断使所有男性患者的血清游离睾酮浓度达到<2.2 pmol/L（正常范围，38 - 114 pmol/L）。血清前列腺特异性抗原活性平均值从130.8±46降至6.9±4.4 ng/mL（P < 0.05）。尽管血清钙、甲状旁腺激素和25 - 羟基维生素D测量值保持不变，但血清骨钙素浓度和尿脱氧吡啶啉排泄率显著增加（分别为P < 0.01）。腰椎QCT平均值从76.5 mg/cm³（95%置信区间[95%CI，57 - 96 mg/cm³]）降至73.9 mg/cm³（95%CI，55 - 93 mg/cm³），下降了6.6±1.5%（P < 0.001），股骨颈DXA平均值从0.94 g/cm²（95%CI，0.81 - 1.07 g/cm²）降至0.91 g/cm²（95%CI，0.79 - 1.04 g/cm²），下降了6.5±1.3%（P < 0.001）。辅助间歇性环磷酰胺治疗后，腰椎QCT平均值增加了7.8±3.7%，最终值为75 mg/cm³（95%CI，48.7 - 101 mg/cm³）（与未进行间歇性环磷酰胺治疗的初始6个月相比，P = 0.001）。在股骨颈和沃德三角区也观察到BMD显著增加。
雄激素受体阻断剂在播散性前列腺癌的治疗中具有既定作用。然而，老年播散性前列腺癌男性患者联合雄激素阻断会导致高骨转换和明显的松质骨丢失。本研究结果表明，间歇性环磷酰胺辅助治疗可能预防这些变化并降低脊柱骨折风险。
