Abstract
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 because of 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 stages 3b to 5, based on two or more estimated glomerular filtration rate measurements less than 45 mL/min/1.73 m2 , aged 40 years or older were identified. New bisphosphonate users were propensity score-matched with up to five non-users to minimize confounding within this population. Our primary outcome was CKD stage worsening (estimated glomerular filtration rate [eGFR] decline or renal replacement therapy). Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcers, and severe hypocalcemia. Hazard ratios (HRs) were estimated using Cox regression and Fine and Gray sub-HRs were calculated for competing risks. We matched 2447 bisphosphonate users with 8931 non-users from CPRD and 1399 users with 6547 non-users from SIDIAP. Bisphosphonate use was associated with greater risk of CKD progression in CPRD (sub-HR [95% CI]: 1.14 [1.04, 1.26]) and SIDIAP (sub-HR: 1.15 [1.04, 1.27]). No risk differences were found for acute kidney injury, gastrointestinal bleeding/ulcers, or hypocalcemia. 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. © 2020 American Society for Bone and Mineral Research (ASBMR).
Highlights
Moderate to severe chronic kidney disease (CKD) affects up to 2.8 million people in the United Kingdom (UK)(1) and 2.7 million people in Spain.[2]. CKD is associated with low bone mass.[3]. Increased fracture risk is associated with increasing CKD severity.[4,5,6,7]
A systematic review of the benefits and harms of antiosteoporosis medications, including bisphosphonates, suggested that bisphosphonates did not increase the risk of renal adverse events (373 patients from four trials), gastrointestinal events (179 patients from two trials), or hypocalcemia (93 patients from one trial).(14) The review acknowledged that most of the included studies had possible reporting bias and that the results might not apply to patients with stages 3b to 5 CKD because of scant evidence in this population
Across 10 imputed data sets, on average 2447 bisphosphonate users were matched with 8931 non-users in Clinical Practice Research Datalink (CPRD) and 1399 users were matched with 6547 non-users in SIDIAP
Summary
Moderate to severe (stages 3 to 5) chronic kidney disease (CKD) affects up to 2.8 million people in the United Kingdom (UK)(1) and 2.7 million people in Spain.[2] CKD is associated with low bone mass.[3] Increased fracture risk is associated with increasing CKD severity.[4,5,6,7]. The most recent (2017) Kidney Disease Outcomes Quality Initiative guidelines[15] proposed that potential kidney progression, the severity of any biochemical abnormalities, fracture risk, and bone and mineral disorders related to CKD should be considered when deciding whether to prescribe bisphosphonates.
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