JNCI：骨靶向药物二膦酸盐类或对乳腺癌治疗有益

当前，我国已进入老龄社会，老年病的防治成为重要的研究课题。其中，老年性骨质疏松症是老年人，尤其是绝经期后妇女的常见病、多发病。

二膦酸盐类药物是近二十年发展起来的一类新药，能防治老年性骨质疏松，其用于临床有如下特点：①不仅能抑制骨吸收，还能增加骨量，使丧失的骨组织恢复；②能促进骨小梁的重建，也能减少吸收陷窝深度；③短期用药，长期显效。

近日，一项研究证实骨靶向药物的一项最新适应症：治疗乳腺癌。癌症患者接受靶向骨的药物二膦酸盐和狄诺塞麦治疗会减少骨吸收，可以减少骨骼并发症的风险，防止恶性骨疾病患者在治疗过程中引发的骨质流失。

此外，这些药物可能会抑制肿瘤细胞和骨细胞之间的“恶性循环”即骨髓微环境内生长因子和细胞因子。药物对干细胞生存环境也有影响，对癌细胞和免疫调节也有直接作用。

在乳腺癌早期阶段（Ⅰ，Ⅱ，Ⅲ期），双磷酸盐类药物唑来膦酸治疗病人后，患者生存期和整体身体质量都得到明显改善。但在晚期乳腺癌阶段，药物治疗并未观察到生存益处。研究人员认为应开展更多研究得到越来越多的证据来支持的骨靶向治疗乳腺癌的功效。

原文摘要：

Effects of Bone-Targeted Agents on Cancer Progression and Mortality

Robert Coleman, Michael Gnant, Gareth Morgan and Philippe Clezardin

Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the “vicious cycle” of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.