Rheumatology Unit, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134, Verona, Italy.
Calcif Tissue Int. 2012 Dec;91(6):395-9. doi: 10.1007/s00223-012-9647-9. Epub 2012 Oct 4.
The aim of this study was to explore whether desensitization to the occurrence of the acute-phase response (APR) in patients previously treated with amino-bisphosphonates (N-BPs) is due to a long-lasting reduction in the number of circulating γδ T cells. Circulating lymphocyte subpopulation counts were obtained from 63 patients with postmenopausal or senile osteoporosis at baseline and after 2 days and 12 months of the first intravenous (IV) 5 mg zoledronic acid (ZOL) infusion. At baseline both the proportion and absolute number of circulating γδ T cells were significantly higher in patients who had never used N-BPs vs. previous users, either oral or IV. A typical APR was observed in none of the patients given IV ZOL a year earlier, in 6 (22 %) of the patients previously treated with oral N-BPs, and in 13 (57 %) of the patients naive to any N-BP treatment. In patients naive to N-BPs, a significant reduction in both total lymphocytes and their subsets was observed 2 days after ZOL infusion; all these changes returned to baseline values 1 year later with the exception of γδ T cells, which remained significantly lower in terms of both proportion and absolute number. These results indicate for the first time that both IV and oral N-BP treatments are associated with a long-lasting decrease in circulating γδ T cells, and this may explain the lower incidence of APR in patients previously exposed to N-BPs. Other clinical implications of this sustained effect of N-BPs on immune-regulatory cells might be important.
本研究旨在探讨先前接受氨基双膦酸盐（N-BP）治疗的患者对急性期反应（APR）发生脱敏是否是由于循环 γδ T 细胞数量的长期减少所致。从 63 名绝经后或老年性骨质疏松症患者中获得基线时以及首次静脉内（IV）5mg唑来膦酸（ZOL）输注后 2 天和 12 个月的循环淋巴细胞亚群计数。基线时，从未使用过 N-BP 的患者与以前使用过 N-BP（无论是口服还是静脉内）的患者相比，循环 γδ T 细胞的比例和绝对数均明显更高。一年前接受静脉内 ZOL 治疗的所有患者均未观察到典型的 APR，6 名（22%）以前接受过口服 N-BP 治疗的患者中有 6 名（22%），13 名（57%）对任何 N-BP 治疗均无经验的患者中有 13 名（57%）。在对 N-BP 无经验的患者中，ZOL 输注后 2 天观察到总淋巴细胞及其亚群均显著减少；所有这些变化在 1 年后均恢复到基线值，除 γδ T 细胞外，其比例和绝对数均明显降低。这些结果首次表明，IV 和口服 N-BP 治疗均与循环 γδ T 细胞的长期减少相关，这可能解释了先前暴露于 N-BP 的患者 APR 发生率较低的原因。N-BP 对免疫调节细胞的这种持续作用的其他临床意义可能很重要。
