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J Bone Miner Res. 2020 Jan 22. doi: 10.1002/jbmr.3961. [Epub ahead of print]

Oral Bisphosphonate Use and All-Cause Mortality in Patients With Moderate-Severe (Grade 3B-5D) Chronic Kidney Disease: A Population-Based Cohort Study.

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Bone Biology Division, Garvan Institute of Medical Research, School of Medicine, University of New South Wales, Sydney, Australia.
Centre for Statistics in Medicine and Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.
Biostatistics Unit, Bellvitge Biomedical Research Institute (IDIBELL) L'Hospitalet de Llobregat, Barcelona, Spain.
Population Health Sciences, University of Bristol, Bristol, UK.
UK Renal Registry, Bristol, UK.
Odense Patient Data Explorative Network, University of Southern Denmark, Odense, Denmark.
Department of Medicine, Holbaek Hospital, Holbaek, Denmark.
Hospital del Mar Institute of Medical Investigation Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), University of Barcelona (UAB), Barcelona, Spain.
Department of Nephrology, Hospital del Mar, Barcelona, Spain.
Clinical School, St Vincent's Hospital, Sydney, Australia.
National Institute for Health Research (NIHR) Biomedical Research Centre Translational Health Sciences, University of Bristol, Bristol, UK.
Medical Research Council (MRC) Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
Grup de Recerca en Epidemiologia de les Malalties Prevalents de l'Aparell Locomotor (GREMPAL) Research Group, Idiap Jordi Gol Primary Care Research Institute, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Universitat Autonoma de Barcelona, Barcelona, Spain.


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.




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