Tramadol in osteoarthritis linked to fewer deaths and fractures than stronger opioids

Design

Retrospective propensity-weighted cohort, US commercial claims 2005 to 2021

Population

1,057,635 adults aged 50 or more with osteoarthritis starting an opioid

Primary outcome

All-cause mortality and fracture

Effect

Tramadol vs hydrocodone: mortality HR 0.81 (0.70 to 0.93); vs oxycodone HR 0.40 (0.34 to 0.47)

This retrospective cohort used US commercial claims from 2005 to 2021 to compare adults aged 50 or more with osteoarthritis who started tramadol, codeine, hydrocodone or oxycodone. Of 1,057,635 patients, mean age 69, 294,760 started tramadol. Propensity score weighting balanced baseline characteristics.

Compared with hydrocodone, tramadol was associated with lower mortality (HR 0.81, 95% CI 0.70 to 0.93) and fewer fractures (HR 0.91, 0.83 to 0.98). Compared with oxycodone, mortality was much lower (HR 0.40, 0.34 to 0.47) and fractures fewer (HR 0.83, 0.75 to 0.93). Against codeine, neither mortality (HR 0.93, 0.73 to 1.19) nor fractures (HR 1.10, 0.96 to 1.25) differed.

The comparison here is only among opioids, so it says nothing about tramadol against non-opioid options, which remain first-line in osteoarthritis. When an opioid is genuinely needed, tramadol looks no worse than codeine and possibly safer than stronger agents, but the very large oxycodone difference suggests prescribers chose oxycodone for sicker patients.

• Use non-opioid treatment, exercise and weight management first in osteoarthritis pain.
• When an opioid is needed, consider tramadol or codeine before stronger opioids in older adults.
• Assess falls risk before starting any opioid, since fractures were common across all groups.
• Check for serotonergic drugs and seizure risk before prescribing tramadol.
• Set a review date and a plan to stop at the start of any opioid course.

Why it matters

Among the opioids used for osteoarthritis pain, the weakest was associated with the fewest serious harms.

Don't overread it

Claims data cannot show tramadol causes fewer deaths; prescribers likely gave stronger opioids to sicker patients.

The statistics, in plain English

A hazard ratio of 0.40 against oxycodone means less than half the mortality rate, but an effect that large in an observational study usually reflects differences in who received each drug that weighting could not remove. The smaller differences against hydrocodone are more plausible as real effects.

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