Confavreux C B, Fontana A, Guastalla J P, Munoz F, Brun J, Delmas P D
INSERM Research Unit 831 and University of Lyon, Rheumatology Department, Hôpital Edouard Herriot, Lyon, France.
Bone. 2007 Sep;41(3):346-52. doi: 10.1016/j.bone.2007.06.004. Epub 2007 Jun 16.
Aromatase inhibitors have demonstrated their superiority to tamoxifen as adjuvant therapy for early breast cancer in postmenopausal women, but are associated with an increased risk of fractures. The aim of our study was to analyze bone loss, bone turnover and their determinants in postmenopausal women treated with anastrozole. We investigated bone loss and bone turnover markers (BTM) in a prospective open cohort study of 118 postmenopausal women treated with anastrozole for an early hormone-dependent breast cancer. Women without osteoporosis were not treated and compared with an age-matched control group of 114 healthy women. Osteoporotic patients (T-score<or=-2.5 S.D.) received weekly risedronate. Bone mineral density (BMD), and the BTM serum osteocalcin and serum C-terminal cross linking telopeptide of type I collagen (CTX) and 17beta-estradiol were measured at baseline and 1 year later. In the surveillance group, anastrozole induced after 1 year of treatment a marked bone loss at the spine (mean+/-S.E.M., [95% confidence interval]) -3.3+/-0.4% [-4.1 to -2.5]), and hip (2.8+/-0.4% [-3.6 to -2]) that was significantly greater than in controls (p<0.0001). Anastrozole induced an increase in bone remodelling: osteocalcin (+36.6%, p<0.0001) and CTX (+34%, p<0.0001). In univariate models, a recent menopause, a low body mass index, a complete chemotherapy (>or=6 courses) and a marked antiestrogenic response--defined by a level of 17beta-estradiol<or=2 pg/ml at 1 year or a decrease >50% between baseline and 1 year--were associated with greater bone loss. In multivariate model, women in the highest quartile of bone loss at the spine (>5.6% at 1 year) and hip (>4.9%) had a marked antiestrogenic response with OR of 10.4 [95% C.I. 1.9-57.2] (p=0.007) and 5.7 [1.3-25] (p=0.024) respectively. Among patients in the surveillance group, those with a normal T-score at both sites (n=46) had also a significant bone loss at spine -3.3+/-0.5% [-4.3 to -2.3], p<0.0001 and at the hip -2.9+/-0.6% [-4.1 to -1.7] p<0.0001. In osteoporotic women treated simultaneously with anastrozole and risedronate, bone loss was prevented at hip, and increased at the spine (+4.1+/-0.9% [2.3 to 5.9], p=0.008), and BTM decreased (-24%, -39% for CTX, p=0.003 and 0.001 vs. changes in the untreated group). Anastrozole increases bone turnover and induces an accelerated bone loss that is significantly related to the suppression of 17beta-estradiol production induced by aromatase inhibitor. The bisphosphonate risedronate prevents anastrozole induced bone loss.
芳香化酶抑制剂已证明其作为绝经后妇女早期乳腺癌辅助治疗药物比他莫昔芬更具优势，但与骨折风险增加相关。我们研究的目的是分析接受阿那曲唑治疗的绝经后妇女的骨质流失、骨转换及其决定因素。我们在一项前瞻性开放队列研究中调查了118例接受阿那曲唑治疗早期激素依赖性乳腺癌的绝经后妇女的骨质流失和骨转换标志物（BTM）。未患骨质疏松症的妇女未接受治疗，并与114名健康女性组成的年龄匹配对照组进行比较。骨质疏松患者（T值≤ -2.5标准差）接受每周一次的利塞膦酸盐治疗。在基线和1年后测量骨矿物质密度（BMD）、BTM血清骨钙素、血清I型胶原C末端交联端肽（CTX）和17β-雌二醇。在监测组中，治疗1年后阿那曲唑导致脊柱明显骨质流失（平均值±标准误，[95%置信区间]）-3.3±0.4% [-4.1至 -2.5]），髋部骨质流失（2.8±0.4% [-3.6至 -2]），显著大于对照组（p < 0.0001）。阿那曲唑导致骨重塑增加：骨钙素增加（+36.6%，p < 0.0001）和CTX增加（+34%，p < 0.0001）。在单变量模型中，近期绝经、低体重指数、完整化疗（≥6个疗程）和明显的抗雌激素反应（定义为1年后17β-雌二醇水平≤2 pg/ml或基线至1年下降>50%）与更大的骨质流失相关。在多变量模型中，脊柱骨质流失最高四分位数（1年后>5.6%）和髋部骨质流失最高四分位数（>4.9%）的女性有明显的抗雌激素反应，脊柱的比值比为10.4 [95%置信区间1.9 - 57.2]（p = 0.007），髋部为5.7 [1.3 - 25]（p = 0.024）。在监测组患者中，两个部位T值正常的患者（n = （此处原文有误，推测可能是46））脊柱也有明显骨质流失 -3.3±0.5% [-4.3至 -2.3]，p < 0.0001，髋部 -2.9±0.6% [-4.1至 -1.7] p < 0.0001。在同时接受阿那曲唑和利塞膦酸盐治疗的骨质疏松女性中，髋部骨质流失得到预防，脊柱骨质流失增加（+4.1±0.9% [2.3至5.9]，p = 0.008），BTM下降（CTX分别下降 -24%、 -39%，与未治疗组变化相比，p = 0.003和0.001）。阿那曲唑增加骨转换并导致加速骨质流失，这与芳香化酶抑制剂诱导的17β-雌二醇生成受抑制显著相关。双膦酸盐利塞膦酸盐可预防阿那曲唑诱导的骨质流失。
