Rates of fractures by medication type in patients with bipolar disorder: A retrospective cohort analysis

This study examined fracture incidence in patients with bipolar disorder compared to those without and assessed fracture risk based on exclusive use of lithium, mood-stabilizing antiepileptics, antipsychotics, or antidepressants versus no medication use.

Using TriNetX, patients aged 18 or older were divided into bipolar and non-bipolar cohorts. The bipolar cohort was subdivided into five sub-cohorts: no medication use, exclusive lithium use, exclusive atypical antipsychotic use, exclusive mood-stabilizing antiepileptics use, and exclusive antidepressant use. The incidence of central, upper extremity, lower extremity, and "any" skeletal fractures (encompassing the previous three groups) were compared between the bipolar and non-bipolar cohorts, between males and females with bipolar disorder, and between patients aged 18-64 and aged 65 or older with bipolar disorder. A second analysis was performed to determine the incidence and relative risk of different fracture types based on exclusive medication use compared to no medication use.

Patients with bipolar disorder had a higher fracture risk than patients without, with an increased risk ranging from 0.43 % for upper extremity fractures to 2.41 % for any fractures. Male patients and patients aged 65 or older had a significantly higher risk of fractures compared to female patients and patients aged 18-64 (p < 0.0001 for all outcomes). Lithium use was associated with a reduced risk of central fractures (p = 0.0065) and any fractures (p = 0.0037). Patients using mood-stabilizing antiepileptics exhibited a lower risk of lower extremity fractures (p = 0.0002) and any fractures (p = 0.0003). Antipsychotic use was linked to a decreased risk of all fracture types (p < 0.0001). Antidepressant use was associated with an increased risk of upper extremity fractures (p < 0.0001) and any fractures (p < 0.0001).

Lithium, mood-stabilizing antiepileptics, and antipsychotics were associated with reduced fracture risk, while antidepressants increased fracture risk. Further research is needed to optimize bipolar disorder treatment strategies while minimizing fracture risk.