bisphosphonates (BPs) are the first-line treatment to prevent fractures in patients with osteoporosis. However, they are contraindicated or used with caution in chronic kidney disease (CKD), mainly because of the lack of evidence of safety and efficacy. This study aimed to investigate the safety of oral BPs in patients with moderate to severe CKD. This study used data from the primary care electronic records system of two cohorts, CPRD GOLD (1997 to 2016) in the UK and SIDIAP (2007 to 2015) in Catalonia, respectively. Where SIDIAP is also associated with end-stage renal disease registry data. CKD stage 3b-5 over 40 years of age [eGFR based on 2 or more glomerular filtration rate estimates<45 ml·min-1• (1.73 m2）-1] were included in the study. The primary outcome was staging worsening of CKD (decreased eGFR or need for renal replacement therapy). Secondary outcomes were acute kidney injury, gastrointestinal bleeding/ulcer, and severe hypocalcemia. The hazard ratio was estimated using the Cox regression model (HR), the competitive risk was calculated using the Fine & Gray model. The investigators matched 2 447 patients with BPs and 8 931 patients without BPs in the CPRD database and 1 399 patients with BPs and 6 547 patients without BPs in SIDIAP. The results showed that BPs use was associated with a higher risk of CKD progression (CPRD:HR =1.14，95%CI：1.04~1.26； SIDIAP:HR=1.15，95%CI: 1.04 to 1.27), but no differences were found in the risk of acute kidney injury, gastrointestinal bleeding/ulcer, or hypocalcemia between the two groups. Therefore, the use of BPs was associated with a mild (15%) increased risk of CKD progression, but no other safety concerns were identified. The results of this study should be referenced before prescribing BPs to patients with moderate to severe CKD.
