Bipolar disorder medications are associated with increased odds of fracture nonunion

The purpose of this study was to assess the odds of nonunion for open and closed fractures in patients with bipolar disorder (BD) and characterize any confounding effect of medication prescription.

This was a retrospective cohort study with data sourced from the TriNetX Research database. Our query was for patients that are ≥ 18 years old with extremity long bone fractures with and without prior BD diagnosis. A 1:1 propensity score matching method, matching for age; sex; nicotine use; long-term NSAID use; long-term opioid use; and prior diagnoses of obesity, osteoporosis, and the Charlson comorbidities, was used to create reference groups. The primary outcome was fracture nonunion. Odds of fracture nonunion of the observed groups were compared to the control groups using an odds ratio (OR) with 95% confidence interval (CI).

A total of 1,824,610 patients with long bone fractures were analyzed, with 2.8% having BD. The nonunion rate was higher in patients with BD (3.9%) than those without BD (3.2%, P < .001). The highest nonunion rates were observed in open fractures at 5.1-16.2%, with no significant difference between patients with and without BD (OR 1.04, 95% CI 0.89-1.22). Closed fractures had nonunion rates of 1.6-5.4%, with BD patients showing 1.30 times higher odds (95% CI 1.21-1.41). In BD patients, having a medication prescription for treatment of BD increased the odds of nonunion in closed fractures by 1.68 times (95% CI 1.50-1.88) when compared to those without medication prescription. When patients prescribed medications were removed, BD patients no longer had significantly different odds of nonunion in closed fractures (OR 1.07, 95% CI 0.95-1.21).

Pharmacological prescriptions for BD, but not BD itself, were associated with significantly increased odds of nonunion in closed fractures, while open fractures were unaffected. Orthopaedic surgeons should consider these increased odds when treating these patients and tailor fracture treatment strategies accordingly.