Intermittent Nitrate Use and Risk of Hip Fracture

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.

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.

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.

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.