A common pain medication—once perceived a safer alternative to many other opioid therapies—is coming under fire once again after results of a recent study suggest tramadol use could negatively impact bone health in older adults.

Less than a year after results of a Mayo Clinic study debunked the perception of tramadol as being less addictive than other pain medications, a new study has found the commonly used pain reliever was linked to a higher risk of hip fractures compared to other medications in more than 140,000 patients.

"Considering the significant impact of hip fracture on morbidity, mortality, and healthcare costs, our results point to the need to consider tramadol's associated risk of fracture in clinical practice and treatment guidelines," said study investigator Guanghua Lei, MD, PhD, of Xiangya Hospital, Central South University, in a statement.

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With an apparent rise in tramadol prescriptions for chronic noncancer pain across the world, investigators sought to further evaluate the safety profile of the treatment—specifically, its association with the risk of hip fracture. To do so, Lei and a team of colleagues from Boston University School of Medicine, the University of California School of Medicine, and Massachusetts General Hospital conducted an analysis of patients in The Health Improvement Network (THIN) database.

In short, the THIN database contained medical records for 17 million individuals from 770 general practice sites across the United Kingdom from 2000 through 2016. The database contained information including patients' anthropometrics, sociodemographics, lifestyle habits, general practitioner visit details, diagnoses from specialists’ evaluations and hospital admissions, as well as laboratory testing results.

For the current analysis, investigators included participants 50 years of age or older with no history of hip fracture, cancer, or opioid use disorder. The primary outcome measure was incident hip fracture during each 1-year follow-up period.

From the 372,372 patients who met inclusion criteria, investigators created 5 propensity score-matched cohorts comparing tramadol use against use of other pain medications. Other pain medications included as comparators in the analysis were codeine, naproxen, ibuprofen, celecoxib, or etoricoxib.

Analyses revealed the risk of hip fracture was higher for tramadol use than in any of the other medication cohorts. Risk of hip fracture was higher in the tramadol cohort than in naproxen (2.9 per 1000 person-years for tramadol versus 1.7 per 1000 person-years for naproxen; HR 1.69, 95% CI, 1.41-2.03), ibuprofen (3.4 per 1000 person-years for tramadol versus 2.0 per 1000 person-years for ibuprofen; HR 1.65, 95% CI, 1.39-1.96), celecoxib (3.4 per 1000 person-years for tramadol versus 1.8 per 1000 person-years for celecoxib; HR 1.85, 95% CI, 1.40-2.44), etoricoxib (2.9 per 1000 person-years for tramadol versus 1.5 per 1000 person-years for etoricoxib; HR 1.96, 95% CI, 1.34-2.87), and codeine (3.7 per 1000 person-years for tramadol versus 2.9 per 1000 person-years for codeine; HR 1.28, 95% CI, 1.13-1.46) cohorts.

Investigators suggested the apparent risk of hip fracture observed in their analyses could be tied to certain side effects of tramadol use—including the risk of seizures, dizziness, or delirium—seen in other studies that could contribute to a higher risk of falls. Additionally, investigators suggest that the results of the study—combined with the potential for negative impact of morbidity, costs, and overall health associated with hip fracture—warrant consideration of tramadol’s associated risk of fracture in clinical practice in treatment guidelines.

This study, “Association of Tramadol Use With Risk of Hip Fracture,” was published online in the Journal of Bone and Mineral Research.