Use of organic nitrates and the risk of hip fracture: A population-based case-control study

Background: The use of organic nitrates has been associated with increased bone mineral density. A large Danish case-control study reported a decreased fracture risk. Other studies have found beneficial effects on bone mineral density with use of rescue (sublingual) or maintenance medication. However, the association with duration of nitrate use and the impact of discontinuation have not been extensively studied. Objectives: To evaluate the association between organic nitrates and hip fracture risk. Methods: A case-control study was conducted using the Dutch PHARMO Record Linkage System (n = 33,104). Cases were patients with a first admission for hip fracture. Up to 4 controls were matched by age, gender and location. Current users of organic nitrates were patients who had received a prescription within 90 days prior to the index date. The analyses were adjusted for disease and drug history. Results: Hip fracture risk was decreased in current users of rescue medication (adjusted [adj.] OR 0.83; 95% CI, 0.63-1.08), when compared to maintenance medication (adj. OR 1.17; 95% CI, 0.97-1.40 [p3 years resulted in an OR of 1.22 [95% CI, 0.84-1.77, p = 0.79]). Hip fracture risk remained steady with a prolonged time since discontinuation. Conclusions: Use of organic nitrates was not associated with a decreased hip fracture risk. The risk was not inversely associated with prolonged nitrate use, which makes a causal effect unlikely. Our findings do not support the use of organic nitrates for the prevention of hip fractures.