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Abstract: PO0569

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

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Potukuchi, Praveen Kumar, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Dashputre, Ankur A., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Thomas, Fridtjof, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Lu, Jun Ling, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Molnar, Miklos Zsolt, University of Utah Health, Salt Lake City, Utah, United States
  • Streja, Elani, University of California Irvine, Irvine, California, United States
  • Kalantar-Zadeh, Kamyar, University of California Irvine, Irvine, California, United States
  • Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background

Diuretics may affect bone metabolism by electrolyte imbalance (e.g., Ca and Na derangements). Inconsistent associations have been reported between diuretic use and risk of fracture, presumably due to the heterogeneity of study designs and populations.

Methods

In a nationwide cohort of 2,318,267 US veterans with an eGFR ≥60 mL/min/1.73m2 from 2004-2006 and follow-up through 2018, we examined the association of incident diuretic use (thiazide, loop, and K-sparing diuretics, as time-dependent exposures) with incidence of any fractures (both vertebral and non-vertebral fractures), using time-dependent Cox models adjusted for sociodemographics, smoking and alcohol use, comorbidities, eGFR, vital signs, and medications (e.g., bone anabolic/antiresorptive agents, SERMs, steroids). Associations were also assessed by diuretic types.

Results

Patients were 59±15 years old; 91% were male; 14% were African American; and 18% were diabetic. Their baseline eGFR was 82±16 mL/min/1.73m2. Among 2,318,267 patients, 835,054 (36.0%) started any diuretic therapy, and 146,017 (6.3%) experienced an incident fracture. After multivariable adjustment, incident diuretic use (vs. non-use) was significantly associated with higher risk of incident fracture (adjusted HR [95%CI], 1.13 [1.06-1.19]). The association was most pronounced for loop diuretics (1.37 [1.28-1.46]) but less evident for thiazide diuretics (1.07 [1.00-1.14]), and was not significant for K-sparing diuretics (1.16 [0.88-1.54]) (Figure).

Conclusion

Diuretic use, particularly loop diuretic use, was independently associated with higher risk of incident bone fractures. While our findings may be from confouding by medical indication, it might suggest a distinct pathogenic contribution of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics.

Funding

  • Veterans Affairs Support