Intermittent Nitrate Use and Risk of Hip Fracture

Am J Med. 2017 Feb;130(2):229.e15-229.e20. doi: 10.1016/j.amjmed.2016.09.006. Epub 2016 Oct 6.

Abstract

Purpose: Nitrates, commonly used antianginal medications, also have a beneficial effect on bone remodeling and bone density, particularly with intermittent use. However, their effect on fracture risk is not clear. We examined the relation of short-acting nitrate use (proxy for intermittent use) with the risk of hip fracture in a large cohort of older adults with ischemic heart disease.

Methods: Participants aged 60 years or more with ischemic heart disease and without a history of hip fracture from The Health Improvement Network, an electronic medical records database in the United Kingdom, were included. The association of incident (new) use of short-acting nitrate formulations (nitroglycerin sublingual/spray/ointment or isosorbide dinitrate injection/sprays) with incident (new-onset) hip fracture risk was examined by plotting Kaplan-Maier curves and calculating hazard ratios using Cox proportional hazards regression models. Competing risk by death was analyzed in separate analyses.

Results: Among 14,451 pairs of matched nitrate users and nonusers (mean age, 72 ± 7.6 years, 41% women for each cohort), 573 fractures occurred during follow-up (257 nitrate users; 316 nonusers). Hip fracture risk was 33% lower among short-acting nitrate users compared with nonusers (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .0008). Competing risk analysis by death did not change effect estimates.

Conclusions: In this large population-based cohort of older adults with ischemic heart disease, we found a significant reduction in hip fracture risk with the use of short-acting nitrates (intermittent use). Future studies are warranted given the potential for nitrates to be potent, inexpensive, and readily available antiosteoporotic agents.

Keywords: Fracture; Intermittent; Nitrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angina, Stable / drug therapy
  • Female
  • Hip Fractures / chemically induced*
  • Humans
  • Isosorbide Dinitrate / adverse effects*
  • Isosorbide Dinitrate / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Myocardial Ischemia / drug therapy
  • Nitroglycerin / adverse effects*
  • Nitroglycerin / therapeutic use
  • Proportional Hazards Models
  • Vasodilator Agents / adverse effects*
  • Vasodilator Agents / therapeutic use

Substances

  • Vasodilator Agents
  • Nitroglycerin
  • Isosorbide Dinitrate