Comparative risks of mortality and fractures in patients with osteoarthritis initiating tramadol versus other opioids

OBJECTIVES: Tramadol is commonly used to manage pain in patients with osteoarthritis, but its comparative safety in this population remains largely unknown. The study aimed to evaluate the risks of all-cause mortality and fracture among patients with osteoarthritis initiating tramadol versus other prescribed opioids. METHODS: We conducted a retrospective cohort study using Optum Clinformatics® Data Mart (2005-2021). Adults aged ≥50 years with osteoarthritis initiating tramadol, codeine, hydrocodone, or oxycodone were included. Outcomes were all-cause mortality and fractures. Propensity score weighting balanced baseline characteristics, and weighted Cox proportional hazards models estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 1,057,635 patients (mean age 69.1 years; 62.5% female), 294,760 initiated tramadol, 97,048 codeine, 474,733 hydrocodone, and 191,094 oxycodone. During follow-up, 9,988 deaths and 10,455 fractures occurred. Tramadol showed similar mortality risk to codeine (HR 0.93, 95% CI 0.73-1.19), but lower risk compared with hydrocodone (HR 0.81, 95% CI 0.70-0.93) and oxycodone (HR 0.40, 95% CI 0.34-0.47). Fracture risk was comparable to codeine (HR 1.10, 95% CI 0.96-1.25) and lower than hydrocodone (HR 0.91, 95% CI 0.83-0.98) and oxycodone (HR 0.83, 95% CI 0.75-0.93). CONCLUSIONS: In adults aged 50 years or older with osteoarthritis initiating an opioid, tramadol initiation was associated with lower risks of mortality and fractures compared with hydrocodone and oxycodone, and similar risks compared with codeine. These findings suggest that tramadol may be a comparatively favorable option when opioid therapy is necessary, although its longer-term comparative safety remains uncertain.