Use of renin-angiotensin system inhibitors is associated with reduction of fracture risk in hemodialysis patients

PLoS One. 2015 Apr 13;10(4):e0122691. doi: 10.1371/journal.pone.0122691. eCollection 2015.


Background: Patients with chronic kidney disease, especially those undergoing dialysis treatment and having secondary hyperparathyroidism, have a high risk of bone fracture. The renin-angiotensin system (RAS) is associated with osteoclastic bone resorption. We aimed to examine whether the use of RAS inhibitors reduces the incidence of fracture in hemodialysis patients.

Methods and findings: This was a multicenter, 3-year, prospective, observational study. From 2008 to 2011, maintenance hemodialysis patients with secondary hyperparathyroidism (N = 3,276) treated with angiotensin converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) at baseline were followed for a mean of 2.7 years. The association between the use of ACEI/ARB and hospitalization rate owing to fracture was examined by using Cox regression models. Effect modifications by the severity of secondary hyperparathyroidism (intact parathyroid hormone [iPTH] level), sex, and systolic blood pressure were also examined. The incidence proportion of fracture-related hospitalization was 5.42% throughout the observation period. ACEI/ARB use was associated with a lower rate of fracture-related hospitalization (adjusted hazard ratio, 0.65; 95% confidence interval [CI], 0.45-0.92). This association was not significantly affected by sex (P = 0.56) or systolic blood pressure levels (P = 0.87). The hazard ratios adjusted by iPTH levels were qualitatively different, but not statistically significant (P = 0.11): 0.77 (95% CI, 0.42-1.39), 0.38 (95% CI, 0.20-0.73), 0.59 (95% CI, 0.29-1.21), and 1.29 (95% CI, 0.58-2.42) for the first, second, third and fourth quartiles of iPTH, respectively.

Conclusions: Use of RAS inhibitors is associated with a lower rate of fracture-related hospitalization in hemodialysis patients with secondary hyperparathyroidism.

Trial registration: NCT00995163.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Female
  • Fractures, Bone / complications
  • Fractures, Bone / drug therapy*
  • Fractures, Bone / pathology
  • Humans
  • Hyperparathyroidism, Secondary / complications
  • Hyperparathyroidism, Secondary / drug therapy*
  • Hyperparathyroidism, Secondary / pathology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / pathology
  • Renin-Angiotensin System / drug effects


  • Angiotensin-Converting Enzyme Inhibitors

Associated data


Grant support

The MBD-5D study was supported by research grants from Kyowa Hakko Kirin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.