Hadji P, Body J-J, Aapro M S, Brufsky A, Coleman R E, Guise T, Lipton A, Tubiana-Hulin M
Department of Gynecology, Philipps-University of Marburg, Marburg, Germany.
CHU Brugmann and Institute J. Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Ann Oncol. 2008 Aug;19(8):1407-1416. doi: 10.1093/annonc/mdn164. Epub 2008 Apr 29.
Recent studies indicate that women with breast cancer are at increased risk of fracture compared with their age-matched peers. Current treatment guidelines are inadequate for averting fractures in osteopenic women, especially those receiving aromatase inhibitor (AI) therapy. Therefore, we sought to identify clinically relevant risk factors for fracture that can be used to assess overall fracture risk and to provide practical guidance for preventing and treating bone loss in women with breast cancer receiving AI therapy.
Systematic review of pertinent information from published literature and meeting abstracts through December 2007 was carried out to identify factors contributing to fracture risk in women with breast cancer. An evidence-based medicine approach was used to select risk factors that can be used to determine when to initiate bisphosphonate treatment of aromatase inhibitor-associated bone loss (AIBL).
Fracture risk factors were chosen from large, well-designed, controlled, population-based trials in postmenopausal women. Evidence from multiple prospective clinical trials in women with breast cancer was used to validate AI therapy as a fracture risk factor. Overall, eight fracture risk factors were validated in women with breast cancer: AI therapy, T-score <-1.5, age >65 years, low body mass index (BMI <20 kg/m(2)), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking. Treatment recommendations were derived from randomized clinical trials.
The authors recommend the following for preventing and treating AIBL in women with breast cancer. All patients initiating AI therapy should receive calcium and vitamin D supplements. Any patient initiating or receiving AI therapy with a T-score >/=-2.0 and no additional risk factors should be monitored every 1-2 years for change in risk status and bone mineral density (BMD). Any patient initiating or receiving AI therapy with a T-score <-2.0 should receive bisphosphonate therapy. Any patient initiating or receiving AI therapy with any two of the following risk factors-T-score <-1.5, age >65 years, low BMI (<20 kg/m(2)), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking-should receive bisphosphonate therapy. BMD should be monitored every 2 years, and treatment should continue for at least 2 years and possibly for as long as AI therapy is continued. To date, the overwhelming majority of clinical evidence supports zoledronic acid 4 mg every 6 months to prevent bone loss in women at high risk. Although there is a trend towards fewer fractures with zoledronic acid, studies completed to date have not been designed to capture significant differences in fracture rate, and longer follow-up is needed.
近期研究表明，与年龄匹配的同龄人相比，乳腺癌女性发生骨折的风险增加。目前的治疗指南不足以预防骨质减少女性发生骨折，尤其是那些接受芳香化酶抑制剂（AI）治疗的女性。因此，我们试图确定临床上与骨折相关的危险因素，这些因素可用于评估总体骨折风险，并为接受AI治疗的乳腺癌女性预防和治疗骨质流失提供实用指导。
对截至2007年12月发表的文献和会议摘要中的相关信息进行系统回顾，以确定导致乳腺癌女性骨折风险的因素。采用循证医学方法选择可用于确定何时开始双膦酸盐治疗芳香化酶抑制剂相关骨质流失（AIBL）的危险因素。
骨折危险因素选自针对绝经后女性的大型、设计良好、有对照、基于人群的试验。来自乳腺癌女性多项前瞻性临床试验的证据用于验证AI治疗作为骨折危险因素。总体而言，在乳腺癌女性中验证了8个骨折危险因素：AI治疗、T值<-1.5、年龄>65岁、低体重指数（BMI<20kg/m²）、髋部骨折家族史、50岁后脆性骨折个人史、口服糖皮质激素使用>6个月以及吸烟。治疗建议源自随机临床试验。
作者对乳腺癌女性预防和治疗AIBL提出以下建议。所有开始AI治疗的患者应补充钙和维生素D。任何开始或接受AI治疗且T值≥-2.0且无其他危险因素的患者应每1 - 2年监测风险状态和骨密度（BMD）变化。任何开始或接受AI治疗且T值<-2.0的患者应接受双膦酸盐治疗。任何开始或接受AI治疗且具有以下任何两个危险因素——T值<-1.5、年龄>65岁、低BMI（<20kg/m²）、髋部骨折家族史、50岁后脆性骨折个人史、口服糖皮质激素使用>6个月以及吸烟——的患者应接受双膦酸盐治疗。应每2年监测BMD，治疗应持续至少2年，可能持续至AI治疗结束。迄今为止，绝大多数临床证据支持每6个月使用4mg唑来膦酸预防高危女性骨质流失。尽管使用唑来膦酸有骨折减少的趋势，但迄今为止完成的研究并非旨在捕捉骨折率的显著差异，需要更长时间的随访。
