Smith Matthew R, Cook Richard J, Coleman Robert, Brown Janet, Lipton Allan, Major Pierre, Hei Yong Jiang, Saad Fred
Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Urology. 2007 Aug;70(2):315-9. doi: 10.1016/j.urology.2007.03.071.
Skeletal complications are a major cause of morbidity in men with hormone-refractory metastatic prostate cancer. These analyses were designed to identify the variables associated with a greater risk of skeletal complications.
The 643 subjects in this report were participants in a randomized placebo-controlled trial to evaluate the effects of zoledronic acid on the incidence of skeletal-related events. All subjects had bone metastases and disease progression despite medical or surgical castration. The relationships between the baseline covariates and the time to the first skeletal-related event were assessed by Cox proportional hazard analyses. The serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide level was assessed as a representative specific marker of osteoblastic and osteoclastic activity, respectively. The other covariates included in the model were age, cancer duration, Eastern Cooperative Oncology Group performance status, analgesic use, and prostate-specific antigen, hemoglobin, and lactate dehydrogenase levels.
Elevated BAP levels were consistently associated with a greater risk of adverse skeletal outcomes. Elevated BAP was significantly associated with a shorter time to the first skeletal-related event on multivariate analyses of the entire study population (relative risk 1.84, 95% confidence interval 1.40 to 2.43; P <0.001) and in subset analyses of the placebo and zoledronic acid groups. Elevated BAP levels were also consistently associated with adverse skeletal outcomes on multivariate analyses of the time to radiotherapy and pathologic fracture, the most common types of skeletal-related events in the study population. No other baseline variable was consistently associated with the risk of adverse skeletal outcomes.
The results of our study have shown that elevated serum BAP levels are associated with a greater risk of adverse skeletal outcomes in men with hormone-refractory prostate cancer and bone metastases.
骨骼并发症是激素难治性转移性前列腺癌男性患者发病的主要原因。这些分析旨在确定与骨骼并发症风险较高相关的变量。
本报告中的643名受试者参与了一项随机安慰剂对照试验，以评估唑来膦酸对骨相关事件发生率的影响。所有受试者尽管接受了药物或手术去势，但仍有骨转移和疾病进展。通过Cox比例风险分析评估基线协变量与首次骨相关事件发生时间之间的关系。血清骨特异性碱性磷酸酶（BAP）和尿N-端肽水平分别作为成骨细胞和成骨细胞活性的代表性特异性标志物进行评估。模型中纳入的其他协变量包括年龄、癌症病程、东部肿瘤协作组（Eastern Cooperative Oncology Group）的体能状态、镇痛药物使用情况，以及前列腺特异性抗原、血红蛋白和乳酸脱氢酶水平。
BAP水平升高始终与不良骨骼结局风险较高相关。在对整个研究人群进行多变量分析时（相对风险1.84，95%置信区间1.40至2.43；P<0.001），以及在安慰剂组和唑来膦酸组的亚组分析中，BAP升高与首次骨相关事件发生时间较短显著相关。在对放疗时间和病理性骨折（研究人群中最常见的骨相关事件类型）进行多变量分析时，BAP水平升高也始终与不良骨骼结局相关。没有其他基线变量始终与不良骨骼结局风险相关。
我们的研究结果表明，血清BAP水平升高与激素难治性前列腺癌和骨转移男性患者不良骨骼结局风险较高相关。
