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Oral Bisphosphonate Use and All-Cause Mortality in Patients With Moderate-Severe (Grade 3B-5D) Chronic Kidney
Dunia Alarkawi1, M Sanni Ali2, Dana Bliuc1
1Bone Biology Division, Garvan Institute of Medical Research, School of Medicine, University of New South Wales, Sydney, Australia.
Insights
Oral bisphosphonates (oBPs) did not increase mortality in patients with moderate-severe chronic kidney disease (CKD). This study found no significant association between oBP use and all-cause mortality in CKD patients, suggesting a potentially safe profile.
Area of Science:
- Nephrology
- Gerontology
- Pharmacology
Background:
- Oral bisphosphonates (oBPs) are linked to reduced fractures and mortality.
- The safety and efficacy of oBPs in patients with moderate-severe chronic kidney disease (CKD) remain unclear.
- CKD is associated with increased fracture risk and mortality, necessitating careful treatment decisions.
Purpose of the Study:
- To investigate the association between oral bisphosphonate (oBP) use and all-cause mortality in patients with moderate-to-severe chronic kidney disease (CKD) stages G3B-5D.
- To evaluate the risks and benefits of oBPs in this specific patient population using real-world data.
Main Methods:
- A population-based cohort study utilizing data from the UK Clinical Practice Research Datalink (CPRD) and the Catalan Information System for Research in Primary Care (SIDIAP).
- Included patients aged 40+ with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m².
- Propensity score (PS) adjustment and trimming were employed to minimize confounding factors and potential biases, modeling oBP use as a time-varying exposure.
Main Results:
- In the CPRD, oBP users showed a non-significant trend towards lower mortality (HR 0.98; 95% CI, 0.94 to 1.04) after PS adjustment and trimming.
- In the SIDIAP, oBPs were not associated with mortality (HR 0.95; 95% CI, 0.89 to 1.01) after PS adjustment and trimming.
- Overall, the study found no significant association between oral bisphosphonate use and increased all-cause mortality in patients with moderate-to-severe CKD.
Conclusions:
- Oral bisphosphonates (oBPs) do not appear to be associated with increased all-cause mortality in patients with moderate-to-severe chronic kidney disease (CKD).
- These findings suggest that oBPs may be a viable treatment option for osteoporosis in CKD patients, although further research is warranted.
- Additional studies are needed to explore other potential effects of oBPs in the CKD population.
Abstract:
Oral bisphosphonates (oBPs) have been associated with reduced fractures and mortality. However, their risks and benefits are unclear in patients with moderate-severe CKD. This study examined the association between oBPs and all-cause mortality in G3B-5D CKD. This is a population-based cohort study including all subjects with an estimated glomerular filtration rate (eGFR) <45/mL/min/1.73 m2 (G3B: eGFR <45/mL/min/1.73 m2 G4: eGFR 15-29/mL/min/1.73 m2 G5: eGFR <15/mL/min/1.73 m2 G5D: hemodialysis) aged 40+ years from the UK Clinical Practice Research Datalink (CPRD) and the Catalan Information System for Research in Primary Care (SIDIAP). Previous and current users of other anti-osteoporosis drugs were excluded. oBP use was modeled as a time-varying exposure to avoid immortal time bias. Treatment episodes in oBP users were created by concatenating prescriptions until patients switched or stopped therapy or were censored or died. A washout period of 180 days was added to (date of last prescription +180 days). Propensity scores (PSs) were calculated using prespecified predictors of mortality including age, gender, baseline eGFR, socioeconomic status, comorbidities, previous fracture, co-medications, and number of hospital admissions in the previous year. Cox models were used for PS adjustment before and after PS trimming (the first and last quintiles). In the CPRD, of 19,351 oBP users and 210,954 non-oBP users, 5234 (27%) and 85,105 (40%) deaths were recorded over 45,690 and 915,867 person-years of follow-up, respectively. oBP users had 8% lower mortality risk compared to non-oBP users (hazard ratio [HR] 0.92; 95% CI, 0.89 to 0.95). Following PS trimming, this became nonsignificant (HR 0.98; 95% CI, 0.94 to 1.04). In the SIDIAP, of 4146 oBP users and 86,127 non-oBP users, 1330 (32%) and 36,513 (42%) died, respectively. oBPs were not associated with mortality in PS adjustment and trimming (HR 1.04; 95% CI, 0.99 to 1.1 and HR 0.95; 95% CI, 0.89 to 1.01). In this observational, patient-based cohort study, oBPs were not associated with increased mortality among patients with moderate-severe CKD. However, further studies are needed on other effects of oBPs in CKD patients. © 2020 American Society for Bone and Mineral Research.
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