Antidepressants with serotonergic effects may be related to possible detrimental effects on bone mineral density (which increases fracture risk). Antidepressants should increase 5-HT signaling to promote bone mass growth; however, many experimental models do not fit that prediction. Studies have found a dose-dependent relationship between risk of fracture in SSRI users in parallel with duration of treatment (Vestergaard et al., 2008).

These results are controversial and require further study to validate that these effects are not a result of depression itself or its symptoms.