Lipton A, Berenson J R
Department of Haematology/Oncology, Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.
Drugs Aging. 1999 Apr;14(4):241-6. doi: 10.2165/00002512-199914040-00001.
Tumour-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by tumour products or indirectly through an influence on other cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Pamidronate is a second-generation amino-bisphosphonate that is a potent inhibitor of osteoclastic activity. In multiple myeloma, a phase III study has shown that the proportion of patients at the end of 21 months who had any skeletal event was significantly lower in the pamidronate group (38%) than in the placebo group (58%). The therapeutic benefit was independent of the type of antimyeloma chemotherapy. Patients who received pamidronate had significant decrease in bone pain and delayed deterioration in performance status and quality of life. Overall there was no survival advantage in patients who received pamidronate. In similar fashion, in 2 phase III breast cancer trials, patients who received pamidronate had fewer skeletal events, decrease in bone pain and analgesic use, and slower deterioration of performance status that in those patients receiving placebo. Again, there was no survival advantage in these patients. Recent studies suggest that the bisphosphonates clodronate can prevent the development of bone metastases in patients with breast cancer.
肿瘤诱导的骨溶解或溶骨性骨病是由破骨细胞激活介导的。破骨细胞可被肿瘤产物直接激活，或通过对其他细胞的影响间接激活。双膦酸盐通过降低破骨细胞活性来抑制骨吸收。帕米膦酸是第二代氨基双膦酸盐，是破骨细胞活性的强效抑制剂。在一项针对多发性骨髓瘤的III期研究中，结果显示，在21个月结束时发生任何骨骼事件的患者比例，帕米膦酸组（38%）显著低于安慰剂组（58%）。治疗益处与抗骨髓瘤化疗的类型无关。接受帕米膦酸治疗的患者骨痛明显减轻，身体状况和生活质量的恶化延迟。总体而言，接受帕米膦酸治疗的患者没有生存优势。同样，在两项III期乳腺癌试验中，接受帕米膦酸治疗的患者骨骼事件较少，骨痛减轻，镇痛药使用减少，身体状况恶化速度比接受安慰剂的患者慢。同样，这些患者也没有生存优势。最近的研究表明，双膦酸盐氯膦酸可以预防乳腺癌患者骨转移的发生。
