Oral bisphosphonates (oBPs) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate-severe CKD. This study examined the association between oBPs and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an estimated glomerular filtration rate (eGFR) <45/mL/min/1.73 m2 (G3B: eGFR <45/mL/min/1.73 m2 G4: eGFR 15-29/mL/min/1.73 m2 G5: eGFR <15/mL/min/1.73 m2 G5D: hemodialysis) aged 40+ years from the UK Clinical Practice Research Datalink (CPRD) and the Catalan Information System for Research in Primary Care (SIDIAP). Previous and current users of other anti-osteoporosis drugs were excluded. oBP use was modeled as a time-varying exposure to avoid immortal time bias. Treatment episodes in oBP users were created by concatenating prescriptions until patients switched or stopped therapy or were censored or died. A washout period of 180 days was added to (date of last prescription +180 days). Propensity scores (PSs) were calculated using prespecified predictors of mortality including age, gender, baseline eGFR, socioeconomic status, comorbidities, previous fracture, co-medications, and number of hospital admissions in the previous year. Cox models were used for PS adjustment before and after PS trimming (the first and last quintiles). In the CPRD, of 19,351 oBP users and 210,954 non-oBP users, 5234 (27%) and 85,105 (40%) deaths were recorded over 45,690 and 915,867 person-years of follow-up, respectively. oBP users had 8% lower mortality risk compared to non-oBP users (hazard ratio [HR] 0.92; 95% CI, 0.89 to 0.95). Following PS trimming, this became nonsignificant (HR 0.98; 95% CI, 0.94 to 1.04). In the SIDIAP, of 4146 oBP users and 86,127 non-oBP users, 1330 (32%) and 36,513 (42%) died, respectively. oBPs were not associated with mortality in PS adjustment and trimming (HR 1.04; 95% CI, 0.99 to 1.1 and HR 0.95; 95% CI, 0.89 to 1.01). In this observational, patient-based cohort study, oBPs were not associated with increased mortality among patients with moderate-severe CKD. However, further studies are needed on other effects of oBPs in CKD patients. © 2020 American Society for Bone and Mineral Research.

中文翻译：

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中重度（3B-5D级）慢性肾脏病患者的口服双膦酸盐使用和全因死亡率：一项基于人群的队列研究。

口服双膦酸盐（oBPs）与降低骨折和死亡率相关。但是，中重度CKD患者的风险和获益尚不清楚。这项研究检查了G3B-5D CKD中oBP与全因死亡率之间的关联。这是一项基于人群的队列研究，包括所有受试者的肾小球滤过率估计值（eGFR）<45 / mL / min / 1.73 m2（G3B：eGFR <45 / mL / min / 1.73 m2 G4：eGFR 15-29 / mL /min/1.73 m2 G5：eGFR <15 / mL / min / 1.73 m2 G5D：血液透析），年龄超过40岁，来自英国临床实践研究数据链（CPRD）和加泰罗尼亚基层医疗研究信息系统（SIDIAP）。排除了其他抗骨质疏松症药物的既往和当前使用者。oBP的使用被建模为随时间变化的暴露，以避免不朽的时间偏差。oBP用户的治疗发作是通过串联处方创建的，直到患者转换或停止治疗或被检查或死亡为止。添加了180天的清除期（最后一次处方的日期+180天）。倾向得分（PSs）使用预先确定的死亡率预测因子进行计算，包括年龄，性别，基线eGFR，社会经济状况，合并症，既往骨折，合并用药以及上一年的住院人数。在PS修整前后（第一个和最后一个五分位），使用Cox模型进行PS调整。在CPRD中，在19,351位oBP用户和210,954位非oBP用户中，分别记录了5234（27％）和85,105（40％）位死亡，随访时间分别超过45,690和915,867人年。与非oBP使用者相比，oBP使用者的死亡率降低了8％（危险比[HR] 0.92； 95％CI为0.89至0。95）。PS修整后，这变得无意义（HR 0.98； 95％CI，0.94至1.04）。在SIDIAP中，在4146位oBP用户和86,127位非oBP用户中，分别有1330位（32％）和36,513位（42％）死亡。oBPs与PS调整和修剪的死亡率无关（HR 1.04； 95％CI，0.99至1.1； HR 0.95； 95％CI，0.89至1.01）。在这项基于患者的观察性队列研究中，中度重度CKD患者的oBP与死亡率增加无关。但是，还需要进一步研究oBPs在CKD患者中的其他作用。©2020美国骨骼和矿物质研究学会。oBPs与PS调整和修剪的死亡率无关（HR 1.04； 95％CI，0.99至1.1； HR 0.95； 95％CI，0.89至1.01）。在这项基于患者的观察性队列研究中，中度重度CKD患者的oBP与死亡率增加无关。但是，还需要进一步研究oBPs在CKD患者中的其他作用。©2020美国骨骼和矿物质研究学会。oBPs与PS调整和修剪的死亡率无关（HR 1.04； 95％CI，0.99至1.1； HR 0.95； 95％CI，0.89至1.01）。在这项基于患者的观察性队列研究中，中度重度CKD患者的oBP与死亡率增加无关。但是，还需要进一步研究oBPs在CKD患者中的其他作用。©2020美国骨骼和矿物质研究学会。