Depression and bone loss: associations, skeletal features and mechanisms from clinical and preclinical studies

Depression has been associated with negative skeletal outcomes, but the specific characteristics and underlying mechanisms remain incompletely understood. This narrative review summarizes clinical and preclinical studies in this field. Current findings suggest that depression may be associated with lower bone mineral density, altered bone remodeling and microarchitecture, and increased risks of falls and fractures. The magnitude and pattern of these associations may vary according to depression severity and chronicity, skeletal site, sex, and life stage. Experimental studies indicate that skeletal changes may involve impaired bone formation, increased bone resorption, or both. Candidate mechanisms include dysregulation of the hypothalamic-pituitary-adrenal axis, sympathetic activation, inflammation, alterations in calcium, vitamin D metabolism, and behavioral and treatment-related factors. Better longitudinal and mechanistic studies are needed to identify patients at greatest skeletal risk.