Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample.

We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index.

In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm²; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm²; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm²; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs—benzodiazepines or antidepressants—were not associated with significantly reduced bone mineral density.

In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.