Gasser Jürg A, Green Jonathan R, Shen Victor, Ingold Peter, Rebmann Andrea, Bhatnagar Ajay S, Evans Dean B
Novartis Institutes for BioMedical Research, Novartis Pharma AG, 4002 Basel, Switzerland.
Bone. 2006 Oct;39(4):787-95. doi: 10.1016/j.bone.2006.04.035. Epub 2006 Jul 17.
Recent evidence has demonstrated that long-term estrogen deprivation using aromatase inhibitor therapy in postmenopausal women with breast cancer results in bone loss and increased fracture risk. Bisphosphonates are potent inhibitors of bone resorption and have demonstrated efficacy in preventing bone loss in postmenopausal women with low bone mineral density (BMD) and in patients with breast cancer receiving estrogen deprivation therapy. Therefore, this study investigated the effects of the bisphosphonate zoledronic acid on BMD and bone strength in rats treated with the aromatase inhibitor, letrozole. Peripheral quantitative computed tomography demonstrated that treatment of rats with daily oral letrozole (1 mg/kg) induced significant bone loss and cortical thinning compared with control animals (P < 0.01). A single prior intravenous dose of zoledronic acid dose dependently protected against letrozole-induced bone loss and cortical thinning, with the highest evaluated dose (20 microg/kg) resulting in BMD values that were not significantly different from controls over the 24 weeks of letrozole treatment. Furthermore, biomechanical testing of the distal femoral metaphysis demonstrated that zoledronic acid (20 microg/kg) significantly prevented the decrease in stiffness and elastic modulus induced by letrozole treatment. Taken together, these data support the use of zoledronic acid for the prevention of bone loss in women with breast cancer receiving aromatase inhibitor therapy.
近期证据表明，在患有乳腺癌的绝经后女性中，使用芳香化酶抑制剂疗法进行长期雌激素剥夺会导致骨质流失并增加骨折风险。双膦酸盐是强效的骨吸收抑制剂，已证明其在预防骨矿物质密度（BMD）低的绝经后女性以及接受雌激素剥夺疗法的乳腺癌患者骨质流失方面具有疗效。因此，本研究调查了双膦酸盐唑来膦酸对接受芳香化酶抑制剂来曲唑治疗的大鼠的骨密度和骨强度的影响。外周定量计算机断层扫描显示，与对照动物相比，每日口服来曲唑（1 mg/kg）治疗的大鼠出现了显著的骨质流失和皮质变薄（P < 0.01）。单次静脉注射唑来膦酸可剂量依赖性地预防来曲唑诱导的骨质流失和皮质变薄，在来曲唑治疗的24周内，评估的最高剂量（20 μg/kg）导致的骨密度值与对照组无显著差异。此外，股骨远端干骺端的生物力学测试表明，唑来膦酸（20 μg/kg）显著预防了来曲唑治疗引起的刚度和弹性模量降低。综上所述，这些数据支持使用唑来膦酸预防接受芳香化酶抑制剂治疗的乳腺癌女性的骨质流失。
