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Bisphosphonates are the first-line treatment for preventing fractures in osteoporosis patients. However, their use is contraindicated or to be used with caution in chronic kidney disease (CKD) patients, primarily due to a lack of information about their safety and effectiveness. We aimed to investigate the safety of oral bisphosphonates in patients with moderate-to-severe CKD. Using primary-care electronic records from two cohorts, CPRD GOLD (1997-2016) and SIDIAP (2007-2015) in the UK and Catalonia, respectively. Both databases were linked to hospital records. SIDIAP was also linked to end-stage renal disease registry data. Patients with CKD stage 3b-5, based on 2 or more estimated glomerular filtration rate measurements less than 45 ml/min/1.73m<sup>2</sup> , aged 40 years or older were identified. New bisphosphonate users were propensity-score-matched with up to five non-users to minimise confounding within this population. Our primary outcome was CKD stage worsening (eGFR decline or renal replacement therapy). Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcers, and severe hypocalcaemia. Hazard ratios (HRs) were estimated using Cox regression and Fine and Gray sub-HRs were calculated for competing risks. We matched 2,447 bisphosphonate users with 8,931 non-users from CPRD and 1,399 users with 6,547 non-users from SIDIAP. Bisphosphonate use was associated with greater risk of CKD progression in CPRD (HR [95% CI]: 1.14 [1.04, 1.26]) and SIDIAP (HR: 1.15 [1.04, 1.27]). No risk differences were found for acute kidney injury, gastrointestinal bleeding/ulcers, or hypocalcaemia. Hence, we can conclude a modest (15%) increased risk of CKD progression was identified in association with bisphosphonate use. No other safety concerns were identified. Our findings should be considered before prescribing bisphosphonates to patients with moderate-to-severe CKD.

Original publication




Journal article


Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Publication Date



Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), Windmill Road, University of Oxford, Oxford, UK.