Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study

Oral Bisphosphonates (oBP) 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 oBP and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an eGFR<45/ml/min/1.73m2 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 modelled 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 (PS) were calculated using pre-specified predictors of mortality including age, gender, baseline eGFR, socio-economic status, co-morbidities, 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, 5,234 (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 (HR 0.92, 95% CI 0.89-0.95). Following PS trimming, this became non-significant (HR 0.98, 95% CI 0.94-1.04). In the SIDIAP, of 4,146 oBP users 86,127 non-oBP users, 1,330 (32%) and 36,513 (42%) died, respectively. oBP were not associated with mortality in PS adjustment and trimming (HR 1.04, 95% CI 0.99-1.1 and HR 0.95, 95% CI 0.89-1.01). In this observational, patient-based cohort study, oBP were not associated with increased mortality amongst patients with moderate-severe CKD. However, further studies are needed on other effects of oBP in CKD patients.