Impact of Bipolar Disorder Medications on Fracture Risk: Insights from a Retrospective Cohort Study

Background and/or Objectives: To analyze fracture incidence in patients with bipolar disorder (BD) compared to those without BD and to characterize fracture risk in patients with BD on exclusive lithium, mood-stabilizing antiepileptic (MSA), antipsychotic, or antidepressant use compared to unmedicated patients with BD.

Design: Retrospective Cohort Study

Setting : TriNetX Database, which includes over 130 million patients across 90 healthcare systems

Participants : Patients aged 18 or older with BD (1,173,795) and without BD (18,168,386) were identified for unmatched analysis, while patients with psychotic disorders, bone malignancies, osteoporosis, and metabolic bone disorders were excluded.

Interventions: not applicable

Main Outcome Measures: Medication categories: no medication, exclusive lithium use, exclusive atypical antipsychotic use, exclusive MSA use, and exclusive antidepressant use. Fracture categories: central fractures, upper extremity fractures, lower extremity fractures, and any fractures.

Results: Patients with BD had significantly higher fracture rates than those without BD (p < 0.0001 for all fracture types). The absolute risk increase for any fracture was 2.41%, for central fractures 2.08%, for upper extremity fractures 0.43%, and for lower extremity fractures 1.20%. When assessing medication effects, lithium was associated with a reduced risk of central fractures (OR 0.66 [0.48-0.89]) and any fractures (OR 0.74 [0.60-0.91]). MSAs were linked to lower extremity fracture reduction (OR 0.79 [0.69-0.89]) and a reduced risk for any fractures (OR 0.86 [0.79-0.93]). Atypical antipsychotics were associated with a decreased risk of all fracture types. Conversely, antidepressant use was linked to an increased risk of upper extremity fractures (OR 1.21 [1.12-1.31]) and any fractures (OR 1.14 [1.08-1.20]).

Conclusions: Lithium and atypical antipsychotics were associated with a decreased risk of fractures, while antidepressants and MSAs were associated with an increased risk of fractures in patients with BD relative to no medication use. Further research is needed to identify the best treatment strategies that lower fracture risk and enhance outcomes for individuals with BD.