Intermittent Nitrate Use and Risk of Hip Fracture

Abstract

Purpose Nitrates, commonly used anti-anginal medications, also have 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) to the risk of hip fracture in a large cohort of older adults with ischemic heart disease. Materials and Methods Participants ≥ 60 years old with ischemic heart disease and without history of hip fracture from The Health Improvement Network (THIN), an electronic medical records database in the UK, were included. The association of incident (new) use of short-acting nitrate formulations (nitroglycerin sublingual/spray/ointment or ISDN injection/sprays) with incident (new-onset) hip fracture risk was examined by plotting Kaplan-Maier curves and calculating Hazard ratios (HR) 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 non-users (mean age 72±7.6, 41% women for each cohort), 573 fractures occurred during follow up (257 nitrate users; 316 non-users). Hip fracture risk was 33% lower among short-acting nitrate users compared with non-users (HR=0.67, 95% CI 0.53–0.85, p=0.0008). Competing risk analysis by death did not change effect estimates. Conclusion In this large population-based cohort of older adults with ischemic heart disease, we found significant reduction in hip fracture risk with use of short-acting nitrates (intermittent use). Future studies are warranted given the potential for nitrates to be potent, inexpensive and readily available anti-osteoporotic agents.

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“…The claims data study examined class of medications rather than specific medications, but reported similar findings for antidepressants; however, our study did not have sufficient numbers of users of medication categories to closely examine many medications. Although a previous study found nitrates to protect against hip fracture, we found use in the past 2 years increased the risk of hip fracture. This could be because of the disease for which they were prescribed (CVD) or because of the hypotensive effects of taking nitrates.…”

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Association of Tramadol Use With Risk of Hip Fracture

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