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While oral bisphosphonates (BP) are commonly used, there is conflicting evidence for their safety in the elderly. Safety concerns might trump BP use in older patients with complex health needs. Our study evaluated the safety of BP, focussing on severe acute kidney injury (AKI), gastrointestinal ulcer (GI ulcer), osteonecrosis of the jaw (ONJ) and femur fractures. We used UK primary care data (CPRD GOLD), linked to hospital (HES inpatient) and ONS mortality data. We included all patients aged >65 with complex health needs and no BP use in the year before study start (01/01/2010). Complex health needs were defined in three cohorts: an electronic frailty index score ≥3 (frailty cohort), ≥1 unplanned hospitalisation/s (hospitalisation cohort); and prescription of ≥10 different medicines in 2009 (polypharmacy cohort). Incidence rates were calculated for all outcomes. Subsequently, all individuals who experienced AKI or GI ulcer anytime during follow-up were included for Self-Controlled Case Series (SCCS) analyses. Incidence rate ratios (IRR) were estimated separately for AKI and GI ulcer, comparing event rates between BP-exposed and unexposed time windows. No SCCS were conducted for ONJ and femur fractures. We identified 94,364 individuals in the frailty cohort, as well as 78,184 and 95,621 persons in the hospitalisation and polypharmacy cohorts. Of those, 3,023, 1,950 and 2,992 individuals experienced AKI and 1,403, 1,019 and 1,453 had GI ulcer/s during follow-up, respectively. Age-adjusted SCCS models found evidence of increased risk of AKI associated with BP use (frailty cohort: IRR 1.65 [95%CI 1.25-2.19]), but no association with GI ulcers (frailty cohort: IRR 1.24 [95%CI 0.86-1.78]). Similar results were obtained for the hospitalisation and polypharmacy cohorts. Our study found a 50-65% increased risk of AKI associated with BP use in elderly patients with complex health needs. Future studies should further investigate the risk-benefit of BP use in these patients. This article is protected by copyright. All rights reserved.

Original publication




Journal article


J bone miner res

Publication Date



AGING, Antiresorptives, General population studies, STATISTICAL METHODS