Academic Department of Clinical Oncology, Weston Park Hospital, Sheffield S10 2SJ, UK.
Eur J Cancer. 2010 May;46(7):1211-22. doi: 10.1016/j.ejca.2010.02.041. Epub 2010 Mar 27.
Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, which is increased when cancer cells invade bone. BPs are an established treatment for cancer that has spread to bone, and effectively reduce pain and other skeletal-related events. New directions in metastatic bone disease (MBD) include personalised BP therapy, such as using bone markers to guide frequency of BP administration and bone targeting agents such as denosumab (AMG 162). Clinical trials strongly suggest that denosumab might play a defined role in the future management of MBD. In terms of potential anti-cancer activity, early data tentatively suggest that zoledronic acid might have a role to play in the prevention of metastatic disease, though whether this is a direct effect on cancer cells, or indirect via the bone marrow micro-environment, or both, is as yet undiscovered. The definitive answer as to the role of adjuvant BP in early cancer is being addressed, with over 20,000 patients with breast, prostate or lung cancer currently participating in adjuvant BP randomised trials. The results of these trials should be available in the next few years, and this will establish whether BPs given early in the course of cancer will be able to prevent the formation of metastases, bone or otherwise.
双膦酸盐（BPs）是一种强效的破骨细胞介导的骨吸收抑制剂，当癌细胞侵犯骨骼时，骨吸收会增加。BPs 是一种已被广泛应用于治疗癌症骨转移的药物，它可以有效减轻疼痛和其他骨骼相关事件。转移性骨疾病（MBD）的新治疗方向包括个性化 BP 治疗，例如使用骨标志物来指导 BP 给药的频率，以及使用骨靶向药物如地舒单抗（AMG 162）。临床试验强烈表明，地舒单抗在未来的 MBD 管理中可能会发挥明确的作用。就潜在的抗癌活性而言，早期数据初步表明唑来膦酸可能在预防转移性疾病方面发挥作用，尽管这是对癌细胞的直接作用，还是通过骨髓微环境的间接作用，或者两者兼有，目前还不得而知。关于辅助性 BP 在早期癌症中的作用的明确答案正在研究中，目前有超过 20000 名患有乳腺癌、前列腺癌或肺癌的患者正在参加辅助性 BP 随机试验。这些试验的结果将在未来几年内公布，这将确定在癌症早期给予 BPs 是否能够预防转移，无论是骨转移还是其他部位的转移。
