Examining depression, antidepressants use, and class and their potential associations with osteoporosis and fractures in adult women: Results from ten NHANES cohorts

Introduction: Osteoporosis, a significant public health concern, affects millions of adult women globally, leading to increased morbidity and fracture risk. Antidepressant use, prevalent in this demographic, is suggested to influence bone mineral density (BMD), yet evidence remains limited across antidepressant classes. Objective/aim: We investigated the association between antidepressant use and osteoporosis in a representative sample of adult women in the United States, focusing on different classes of antidepressants and their potential associations with BMD and fracture risk. Methods: We conducted a cross-sectional analysis using data from ten cohorts of the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2000 to 2017-2020. The sample included adult women, with data collected on antidepressant use, BMD scores, and reported fractures. Statistical models adjusted for potential confounders such as Major Depressive Disorder (MDD), age, physical activity, and comorbidities. Results: Antidepressant use was associated with a 44 % increase in the odds of osteoporosis. Phenylpiperazines showed the highest association, followed by miscellaneous antidepressants and tricyclic antidepressants (TCAs). Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) also demonstrated significant, though comparatively lower associations. The odds of fractures were elevated by 62 % among antidepressant users, particularly with phenylpiperazines and miscellaneous antidepressants. A doseresponse analysis indicated that both the number and duration of antidepressants were associated with increased odds of osteoporosis. Conclusion: Our findings underscore the need for heightened awareness of the adverse effects of antidepressants on bone health, particularly in adult women. Careful consideration is necessary when prescribing these medications, especially in populations at risk for osteoporosis and MDD.