Sedative-hypnotic use and its association with osteoporosis and fractures: a national analysis, 1999–2020

Sedative-hypnotics are widely prescribed in adults, yet their skeletal effects remain unclear. In US adults, use was associated with higher odds of osteoporosis and fractures, with greater odds over longer duration. Further longitudinal and mechanistic studies are warranted to clarify temporal relationships and the biological pathways underlying these associations. PURPOSE: To examine the associations between sedative-hypnotic use and osteoporosis and fractures among adults, evaluating variations in drug class and duration while accounting for key confounders. METHODS: We conducted a cross-sectional analysis of eight NHANES cycles (1999-2010, 2013-2014, 2017-2020), including adults ≥ 20 years with bone mineral density (BMD), osteoporosis status, prescription data, and complete covariates. Sedative-hypnotic use (benzodiazepines, Z-drugs, barbiturates) and duration were identified through self-reported prescriptions. Osteoporosis was defined by DXA femoral neck T-scores ≤ -2.5 or self-reported physician diagnosis, while fractures were defined as self-reported hip, wrist, or spine fractures resulting from a fall from standing height or less. Multivariable logistic regression estimated associations with osteoporosis and fractures, adjusting for demographic, socioeconomic, lifestyle, clinical, and medication-related factors. Analyses were stratified by sedative-hypnotic class. RESULTS: Sedative-hypnotic use was associated with increased odds of osteoporosis, strongest for barbiturates (OR 2.57, 95% CI 1.09-6.07), Z-drugs (OR 1.93, 95% CI 1.44-2.59), and benzodiazepines (OR 1.36, 95% CI 1.12-1.63). Osteoporosis odds increased by 3% per year of use, corresponding to a 21.9% relative increase over 10 years. The association with fractures was strongest for Z-drugs (OR 1.89, 95% CI 1.11-3.19) and benzodiazepines (OR 1.53, 95% CI 1.11-2.12), with a 30% relative increase in fracture probability over 10 years. CONCLUSION: Sedative-hypnotic use was associated with higher odds of osteoporosis and fractures, with class-specific and duration-dependent associations. These findings warrant further longitudinal and mechanistic studies to clarify the temporal relationships and underlying mechanisms linking sedative-hypnotic use, osteoporosis, and fractures.