Hip Fracture Risk After Treatment with Tramadol or Codeine: An Observational Study

INTRODUCTION: Hip fractures among older people are a major public health issue, which can impact quality of life and increase mortality within the year after they occur. A recent observational study found an increased risk of hip fracture in subjects who were new users of tramadol compared with codeine. These drugs have somewhat different indications. Tramadol is indicated for moderate to severe pain and can be used for an extended period; codeine is indicated for mild to moderate pain and cough suppression. OBJECTIVE: In this observational study, we compared the risk of hip fracture in new users of tramadol or codeine, using multiple databases and analytical methods. METHODS: Using data from the Clinical Practice Research Datalink and three US claims databases, we compared the risk of hip fracture after exposure to tramadol or codeine in subjects aged 50–89 years. To ensure comparability, large-scale propensity scores were used to adjust for confounding. RESULTS: We observed a calibrated hazard ratio of 1.10 (95% calibrated confidence interval 0.99–1.21) in the Clinical Practice Research Datalink database, and a pooled estimate across the US databases yielded a calibrated hazard ratio of 1.06 (95% calibrated confidence interval 0.97–1.16). CONCLUSIONS: Our results did not demonstrate a statistically significant difference between subjects treated for pain with tramadol compared with codeine for the outcome of hip fracture risk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-022-01198-9.