Greenspan Susan L, Nelson Joel B, Trump Donald L, Wagner Julie M, Miller Megan E, Perera Subashan, Resnick Neil M
Divisions of Geriatric Medicine and Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, PA 15213-3221, USA.
J Clin Oncol. 2008 Sep 20;26(27):4426-34. doi: 10.1200/JCO.2007.15.1233.
Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT.
A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers.
Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% +/- 0.7) and hip (mean, 1.3% +/- 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, -1.9% +/- 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (+/- 1.2%) increase at the spine and a 3.2% (+/- 1.5%) at the hip (both P < .05). Bone turnover remained suppressed.
Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health.
前列腺癌的雄激素剥夺疗法（ADT）与骨质流失和骨质疏松性骨折相关。我们的目标是研究在接受ADT的男性中，持续、停用或延迟口服双膦酸盐治疗时骨密度和骨转换的变化。
在一项双盲、部分交叉试验中，共有112例接受ADT的非转移性前列腺癌男性被随机分配至每周一次阿仑膦酸钠70mg组或安慰剂组，在第2年对最初接受活性治疗的患者进行第二次随机分配。结果包括骨矿物质密度和骨转换标志物。
最初随机分配至阿仑膦酸钠组且在第2年随机重新分配继续治疗的男性，脊柱骨密度进一步增加（平均2.3%±0.7），髋部骨密度增加（平均1.3%±0.5%；P均＜0.01）；第2年随机分配至安慰剂组的男性，脊柱和髋部骨密度维持不变，但前臂骨密度降低（平均-1.9%±0.6%；P＜0.01）。第2年随机分配开始使用阿仑膦酸钠的患者，脊柱和髋部骨量有所改善，但与基线时开始使用阿仑膦酸钠的患者相比，增加幅度较小。接受阿仑膦酸钠治疗2年的男性，脊柱平均增加6.7%（±1.2%），髋部增加3.2%（±1.5%）（P均＜0.05）。骨转换仍受到抑制。
在接受ADT的非转移性前列腺癌男性中，每周一次阿仑膦酸钠可提高骨密度并降低骨转换。阿仑膦酸钠治疗的第二年可带来额外的骨骼益处，而停药则会导致骨质流失和骨转换增加。延迟双膦酸盐治疗似乎对骨骼健康有害。
