Psychotropic medication use and bone fracture risk among patients with multiple sclerosis: a real-world study

In this global real-world study, psychotropic medications, particularly analgesics, were associated with increased risks of fractures (HR, 2.41; P < 0.001) and disease relapse (HR, 3.63; P < 0.001) in patients with multiple sclerosis. Interaction analyses further indicated a higher fracture risk among opioid users (HR, 3.83; P < 0.001).

Patients with multiple sclerosis (MS) frequently require psychotropic medications, yet their effects on fracture risk and disease activity remain unclear. This study evaluated the risks of fractures, MS relapse, and mortality associated with psychotropic medication use in patients with MS.

We conducted a global, retrospective cohort study using the TriNetX Research Network. Adult patients with MS were categorized into a psychotropics group and a control group. Propensity score matching in a 1:1 ratio was performed to balance baseline covariates. Primary outcomes included risks of all fractures (hip, vertebral, and extremity), MS relapse, and mortality assessed over a 5-year follow-up. Interaction analyses were performed to determine the differential effects of medication classes.

After matching, 117,534 patients (58,777 per group) were included. At the 5-year follow-up, the psychotropic users exhibited significantly higher risks of all fractures (HR, 2.41; 95% CI 2.22-2.63; NNH, 49) and MS relapse (HR, 3.63; 95% CI 3.51-3.75; NNH, 6). No significant difference was observed in mortality. Interaction testing revealed that analgesic use was the primary contributor to fracture risk. Subgroup analysis further identified opioids as the high-risk agent (HR, 3.83; 95% CI 3.45-4.25; NNH, 24), whereas non-opioid analgesics showed no significant association with overall fracture risk.

Psychotropic medication use was associated with increased fracture and relapse risk in multiple sclerosis, driven primarily by opioid analgesics, without an effect on mortality. Bone-conscious pain management and fall prevention should be prioritized.