Incident Diuretic Use and Subsequent Risk of Bone Fractures: A Large Nationwide Observational Study of US Veterans

Keiichi Sumida; Prabin Shrestha; Yamini Mallisetty; Satya Surbhi; Fridtjof Thomas; Elani Streja; Kamyar Kalantar-Zadeh; Csaba P Kovesdy

doi:10.1016/j.mayocp.2023.09.018

Incident Diuretic Use and Subsequent Risk of Bone Fractures: A Large Nationwide Observational Study of US Veterans

Mayo Clin Proc. 2024 Apr 3:S0025-6196(23)00466-4. doi: 10.1016/j.mayocp.2023.09.018. Online ahead of print.

Authors

Keiichi Sumida¹, Prabin Shrestha¹, Yamini Mallisetty¹, Satya Surbhi², Fridtjof Thomas³, Elani Streja⁴, Kamyar Kalantar-Zadeh⁴, Csaba P Kovesdy⁵

Affiliations

¹ Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
² Center for Health System Improvement, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
³ Division of Biostatistics, Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
⁴ Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange, CA, USA; Tibor Rubin Veterans Affairs Medical Center, Long Beach, CA, USA.
⁵ Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA; Nephrology Section, Memphis VA Medical Center, Memphis, TN, USA. Electronic address: ckovesdy@uthsc.edu.

PMID: 38573302
DOI: 10.1016/j.mayocp.2023.09.018

Abstract

Objective: To investigate the association of incident use of diuretics with subsequent risk of incident bone fractures.

Patients and methods: In a nationwide cohort of 863,339 US veterans receiving care from the VA health care system between October 1, 2004, and September 30, 2006, with follow-up through June 30, 2018, we examined the association of incident diuretic use (overall, and separately by thiazide, loop, and potassium-sparing diuretics) with subsequent risk of incident bone fractures using multivariable Cox regression models while minimizing confounding by indication using a target trial emulation approach.

Results: Patients were 63.3±12.9 years old; 93.5% (n=807,180) were male; and 27.1% (n=233,996) were diabetic. Their baseline estimated glomerular filtration rate was 84.4±16.5 mL/min per 1.73 m². Among 863,339 patients, 424,386 (49.2%) newly initiated diuretics, of which 77.4% (n=328,524), 22.5% (n=95,457), and 0.1% (n=405) were thiazide, loop, and potassium-sparing diuretic users, respectively. After multivariable adjustments, incident diuretic use (vs non-use) was significantly associated with higher risk of incident fracture (adjusted HR [aHR], 1.14; 95% CI, 1.11 to 1.16). The association was most pronounced for loop diuretics (aHR, 1.39; 95% CI, 1.35 to 1.44) but less evident for thiazide diuretics (aHR, 1.08; 95% CI, 1.06 to 1.10) and was not significant for potassium-sparing diuretics (aHR, 0.97; 95% CI, 0.62 to 1.52). The diuretic-fracture association was more evident in younger (vs older) patients, those with (vs without) corticosteroid use, and those with lower (vs higher) serum sodium levels.

Conclusion: Incident use of diuretics, particularly loop diuretics, was independently associated with higher risk of incident bone fractures. Our findings suggest distinct pathophysiologic contributions of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics.

Published by Elsevier Inc.