接受促性腺激素释放激素激动剂治疗的前列腺癌男性患者的骨质流失

Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists.

作者信息

Stoch S A, Parker R A, Chen L, Bubley G, Ko Y J, Vincelette A, Greenspan S L

机构信息

Division of Bone and Mineral Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

出版信息

J Clin Endocrinol Metab. 2001 Jun;86(6):2787-91. doi: 10.1210/jcem.86.6.7558.

DOI:10.1210/jcem.86.6.7558

PMID:11397888

Abstract

Prostate cancer is the most common visceral malignancy in men. As the tumor is testosterone dependent, a frequent treatment modality involves therapy with GnRH agonists (GnRH-a) resulting in hypogonadism. Because testosterone is essential for the maintenance of bone mass in men, we postulated that GnRH-a therapy would negatively impact skeletal integrity. We compared bone mineral density (BMD), biochemical markers of bone turnover, and body composition in 60 men with prostate cancer (19 men receiving GnRH-a therapy and 41 eugonadal men) and BMD in 197 community-living healthy controls of similar age. BMD was assessed by dual energy x-ray absorptiometry and ultrasound. Biochemical markers of bone turnover, included markers of bone resorption (urinary N-telopeptide) and bone formation markers (bone-specific alkaline phosphatase and osteocalcin). Body composition (total body fat and lean body mass) was assessed by dual energy x-ray absorptiometry. Significantly lower BMD was found at the lateral spine (0.69 +/- 0.17 vs. 0.83 +/- 0.20 g/cm(2); P < 0.01), total hip (0.94 +/- 0.14 vs. 1.05 +/- 0.16 g/cm(2); P < 0.05), and forearm (0.67 +/- 0.11 vs. 0.78 +/- 0.07 g/cm(2); P < 0.01) in men receiving GnRH-a compared with the eugonadal men with prostate cancer. Significant differences were also seen at the total body, finger, and calcaneus (all P < 0.01). BMD values in eugonadal men with prostate cancer and healthy controls were similar. Markers of bone resorption (urinary N-telopeptide) and bone formation (bone-specific alkaline phosphatase) were elevated in men receiving GnRH-a therapy compared with those in eugonadal men with prostate cancer. Men receiving GnRH-a also had a higher percent total body fat (29 +/- 5% vs. 25 +/- 5%; P < 0.01) and lower percent lean body weight (71 +/- 5% vs. 75 +/- 5%; P < 0.01) compared with eugonadal men with prostate cancer. In conclusion, men with prostate cancer receiving androgen deprivation therapy have a significant decrease in bone mass and increase in bone turnover, thus placing them at increased risk of fracture.

摘要

前列腺癌是男性最常见的内脏恶性肿瘤。由于该肿瘤依赖睾酮，一种常见的治疗方式是使用促性腺激素释放激素激动剂（GnRH-a）进行治疗，这会导致性腺功能减退。因为睾酮对维持男性骨量至关重要，我们推测GnRH-a治疗会对骨骼完整性产生负面影响。我们比较了60名前列腺癌男性（19名接受GnRH-a治疗的男性和41名性腺功能正常的男性）的骨矿物质密度（BMD）、骨转换生化标志物和身体成分，以及197名年龄相仿的社区居住健康对照者的BMD。BMD通过双能X线吸收法和超声进行评估。骨转换生化标志物包括骨吸收标志物（尿N-端肽）和骨形成标志物（骨特异性碱性磷酸酶和骨钙素）。身体成分（全身脂肪和瘦体重）通过双能X线吸收法进行评估。与性腺功能正常的前列腺癌男性相比，接受GnRH-a治疗的男性在腰椎侧位（0.69±0.17 vs. 0.83±0.20 g/cm²；P<0.01）、全髋部（0.94±0.14 vs. 1.05±0.16 g/cm²；P<0.05）和前臂（0.67±0.11 vs. 0.78±0.07 g/cm²；P<0.01）的BMD显著降低。在全身、手指和跟骨处也观察到显著差异（均P<0.01）。性腺功能正常的前列腺癌男性和健康对照者的BMD值相似。与性腺功能正常的前列腺癌男性相比，接受GnRH-a治疗的男性的骨吸收标志物（尿N-端肽）和骨形成标志物（骨特异性碱性磷酸酶）升高。与性腺功能正常的前列腺癌男性相比，接受GnRH-a治疗的男性的全身脂肪百分比也更高（29±5% vs. 25±5%；P<0.01），瘦体重百分比更低（71±5% vs. 75±5%；P<0.01）。总之，接受雄激素剥夺治疗的前列腺癌男性骨量显著下降，骨转换增加，因此骨折风险增加。