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Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study

Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study
Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study

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 m 2 (G3B: eGFR <45/mL/min/1.73 m 2 G4: eGFR 15–29/mL/min/1.73 m 2 G5: eGFR <15/mL/min/1.73 m 2 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.

BISPHOSPHONATES, CHRONIC KIDNEY DISEASE, EPIDEMIOLOGY, MORTALITY, OSTEOPOROSIS
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894-900
Alarkawi, Dunia
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Ali, M. Sanni
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Bliuc, Dana
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Pallares, Natalia
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Tebé, Cristian
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Ellhussein, Leena
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Caskey, Fergus J.
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Arden, Nigel K.
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Ben-Shlomo, Yoav
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Abrahamsen, Bo
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Diez-Perez, A.
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Pascal, Julio
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Perez-Saez, Maria Jose
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Center, Jacqueline R.
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Judge, Andrew
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Cooper, Cyrus
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Javaid, Muhammad K.
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Prieto-Alhambra, Daniel
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Alarkawi, Dunia
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Ali, M. Sanni
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Bliuc, Dana
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Pallares, Natalia
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Tebé, Cristian
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Ellhussein, Leena
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Caskey, Fergus J.
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Arden, Nigel K.
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Ben-Shlomo, Yoav
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Abrahamsen, Bo
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Diez-Perez, A.
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Pascal, Julio
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Perez-Saez, Maria Jose
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Center, Jacqueline R.
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Judge, Andrew
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Cooper, Cyrus
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Javaid, Muhammad K.
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Prieto-Alhambra, Daniel
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Alarkawi, Dunia, Ali, M. Sanni, Bliuc, Dana, Pallares, Natalia, Tebé, Cristian, Ellhussein, Leena, Caskey, Fergus J., Arden, Nigel K., Ben-Shlomo, Yoav, Abrahamsen, Bo, Diez-Perez, A., Pascal, Julio, Perez-Saez, Maria Jose, Center, Jacqueline R., Judge, Andrew, Cooper, Cyrus, Javaid, Muhammad K. and Prieto-Alhambra, Daniel (2020) Oral bisphosphonate use and all-cause mortality in patients with moderate-severe (grade 3B-5D) chronic kidney disease: a population-based cohort study. Journal of Bone and Mineral Research, 35 (5), 894-900. (doi:10.1002/jbmr.3961).

Record type: Article

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 m 2 (G3B: eGFR <45/mL/min/1.73 m 2 G4: eGFR 15–29/mL/min/1.73 m 2 G5: eGFR <15/mL/min/1.73 m 2 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.

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Alarkawi_et_al-2020-Journal_of_Bone_and_Mineral_Research - Accepted Manuscript
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Accepted/In Press date: 2 January 2020
e-pub ahead of print date: 22 January 2020
Published date: May 2020
Keywords: BISPHOSPHONATES, CHRONIC KIDNEY DISEASE, EPIDEMIOLOGY, MORTALITY, OSTEOPOROSIS

Identifiers

Local EPrints ID: 437423
URI: http://eprints.soton.ac.uk/id/eprint/437423
ISSN: 0884-0431
PURE UUID: e03b52f1-6edc-4ec4-9bd8-5ecfe645f5e3
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 29 Jan 2020 17:37
Last modified: 26 Nov 2021 07:14

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Contributors

Author: Dunia Alarkawi
Author: M. Sanni Ali
Author: Dana Bliuc
Author: Natalia Pallares
Author: Cristian Tebé
Author: Leena Ellhussein
Author: Fergus J. Caskey
Author: Nigel K. Arden
Author: Yoav Ben-Shlomo
Author: Bo Abrahamsen
Author: A. Diez-Perez
Author: Julio Pascal
Author: Maria Jose Perez-Saez
Author: Jacqueline R. Center
Author: Andrew Judge
Author: Cyrus Cooper ORCID iD
Author: Muhammad K. Javaid
Author: Daniel Prieto-Alhambra

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