In patients with moderate to severe chronic kidney disease (CKD 3B-5D), oral bisphosphonate treatment was not associated with increased all-cause mortality risk, and may even be associated with decreased mortality risk in some cases, according to study results published in the Journal of Bone and Mineral Research.
Patients with CKD grade 3B to 5D are at increased risk for fracture, and although oral bisphosphonates have been associated with reduced fracture risk and mortality in the general population, limited data are available on these treatment effects in patients with moderate to severe CKD. The goal of the current study was to explore the association between oral bisphosphonates and all-cause mortality in this population of patients.
The population-based cohort study included patients aged ≥40 years with an estimated glomerular filtration rate <45 mL/min/1.73 m2. The study used data from 2 populations: patients from the United Kingdom Clinical Practice Research Datalink (CPRD) and the Catalan SIDIAP (Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària). The primary outcome was all-cause mortality.
The analyses included 19,351 oral bisphosphonate users and 210,954 nonusers from the CPRD database and 4146 users and 86,127 nonusers from the SIDIAP database.
In the CPRD cohort, there were 5234 (27%) and 85,105 (40%) deaths recorded over the course of 45,690 and 915,867 person-years of follow-up in oral bisphosphonate users and nonusers, respectively (absolute mortality rates, 11.5/100 and 9.3/100 person-years, respectively). Although unadjusted analysis demonstrated a significantly increased mortality risk among oral bisphosphonate users compared with nonusers (hazard ratio [HR], 1.25; 95% CI, 1.22-1.29), after multivariable adjustment, mortality risk was lower among oral bisphosphonate users than nonusers (HR, 0.92; 95% CI, 0.90-0.95).
The protective effect of oral bisphosphonates was more significant among women (HR, 0.89 [95% CI, 0.85-0.92] vs 1.03 [95% CI, 1.00-1.06] for men), patients with a history of prior fracture (HR, 0.80 [95% CI, 0.74-0.85] vs 0.94 [95% CI, 0.91-0.98] for those with no history of fracture), and patients with CKD grade 4 or 5 on dialysis (HR, 0.70 [95% CI, 0.65-0.72] vs 0.96 [95% CI, 0.93-0.99] for those with CKD grade 3B).
In the SIDIAP, there were 1330 (32%) and 36,513 (42%) deaths recorded over the course of 14,374 and 344,389 person-years of follow-up in oral bisphosphonate users and nonusers, respectively (absolute mortality rates, 9.3/100 and 10.6/100 person-years, respectively).
In this cohort, the unadjusted analysis showed an 11% decreased mortality risk (HR, 0.89; 95% CI, 0.84-0.93) in oral bisphosphonate users, but propensity-score adjusted analysis showed no association between oral bisphosphonate use and mortality risk. No significant effect of sex, history of prior fracture, or CKD grade was seen.
The study had several limitations, including the observational design and potential related biases and residual confounders, as well as lack of assessment of associations between incident fracture and mortality in the study populations and no data on cardiovascular events, which are the main cause of mortality in patients with CKD.
“[O]ral bisphosphonate treatment in patients with G3B-5D CKD was not associated with increased mortality risk. It may be associated with a decreased mortality risk especially in women, those with prior history of fracture and those with G4-5D CKD,” concluded the researchers.
Alarkawi D, Ali MS, Bliuc D, et al. Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study [published online January 22, 2020]. J Bone Miner Res. doi:10.1002/jbmr.3961