OBJECTIVES: Both increased age and type-2 diabetes are risk factors for developing bone fractures. While recent data in elderly diabetic individuals suggest a link between hypoglycemia and elevated risk of fall-related fractures, the association between sulfonylureas (SU), commonly used hypoglycemic agents, and fracture risk is not well investigated. METHODS: We conducted a study to evaluate the association between SU and risk of developing hip fracture using Ingenix® data (2002-05). The analysis included elderly individuals aged ≥65 years (47.9% females) on oral treatment for diabetes (insulin users excluded), classified as SU users (n=20,741) and non-users (n=22,114) at baseline. RESULTS: During the follow-up, we identified 420 cases of incident hip fractures in the SU group and 228 in non-SU group; unadjusted odds ratio (OR) for hip fracture risk was 1.98 (95% confidence intervals [CI]:1.69-2.33). In a multivariable logistic regression analysis simultaneously accounting for propensity to use SU and for potential confounders (age, gender, health insurance, geographic region, CVD, stroke, osteoporosis, dementia, hypertension, and use of steroids, benzodiazepines, anti-depression, anti-psychotic, anti-convulsant therapy and treatment for osteoporosis), the adjusted OR was 1.60 (95%CI: 1.35-1.90). This association was similar among men (210 cases; OR=1.68; 95%CI: 1.24-2.26) and women (438 cases; OR: 1.56; 95%: 1.27-1.92). In addition, SU users also had higher risk of hypoglycemia compared to non-users (5.8% vs. 2.1%). Furthermore, hypoglycemia was more common among hip fracture cases (12.0%) compared to non-cases (3.8%); the multivariable OR for hypoglycemia-fracture association adjusted for the above covariates was 1.81 (95% CI: 1.40-2.34). CONCLUSIONS: These results suggest that SU may be associated with increased risk of hip fracture in elderly men and women with diabetes, possibly related to elevated risk of hypoglycemia-induced falls. These findings need to be confirmed in future studies which should also further investigate the interrelationships of SU use with hypoglycemia, falls and fractures.