Increased Fracture Risk with Furosemide Use in Children with Congenital Heart Disease

J Pediatr. 2018 Aug;199:92-98.e10. doi: 10.1016/j.jpeds.2018.03.077. Epub 2018 May 9.


Objectives: To determine the association of furosemide therapy with the incidence of bone fractures in children with congenital heart disease.

Study design: We conducted a retrospective cohort study with data extracted from the 2008-2014 Texas Medicaid databases. Pediatric patients aged <12 years diagnosed with congenital heart disease, cardiomyopathy, or heart failure were included. Patients taking furosemide were categorized into a furosemide-adherent group (medication possession ratio of ≥70%), and a furosemide-nonadherent group (medication possession ratio of <70%). A third group of patients was matched to the furosemide user groups by using propensity score matching. A multivariate logistic regression and Cox proportional hazard model with a Kaplan-Meier plot (time-to-fracture) were used to compare the 3 groups, controlling for baseline demographics and clinical characteristics.

Results: After matching, 3912 patients (furosemide adherent, n = 254; furosemide nonadherent, n = 724; no furosemide, n = 2934) were identified. The incidence of fractures was highest for the furosemide-adherent group (9.1%; 23 of 254), followed by the furosemide-nonadherent group (7.2%; 52 of 724), which were both higher than for patients who did not receive furosemide (5.0%; 148 of 2934) (P < .001). Using logistic regression, both furosemide groups were more likely to have fractures than the no furosemide group: furosemide-adherent OR of 1.9 (95% CI, 1.17-2.98; P = .009); furosemide nonadherent OR of 1.5 (95% CI, 1.10-2.14; P = .01). In the Cox proportional hazard model, the risk of fractures for the furosemide-adherent group was significantly higher compared with the no furosemide group (HR, 1.6; 95% CI, 1.00-2.42; P = .04).

Conclusions: Furosemide therapy, even with nonconsistent dosing, was associated with an increased risk of bone fractures in children with congenital heart disease.

Keywords: congenital heart disease; fractures; furosemide; loop diuretic.

Publication types

  • Multicenter Study

MeSH terms

  • Child
  • Child, Preschool
  • Diuretics / adverse effects
  • Diuretics / therapeutic use
  • Female
  • Follow-Up Studies
  • Fractures, Bone / chemically induced*
  • Fractures, Bone / epidemiology
  • Furosemide / adverse effects*
  • Furosemide / therapeutic use
  • Heart Defects, Congenital / drug therapy*
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Medication Adherence*
  • Propensity Score*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • United States / epidemiology


  • Diuretics
  • Furosemide