Association of Tramadol Use With Risk of Hip Fracture

Abstract

Several professional organizations have recommended tramadol as one of the first‐line or second‐line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000–2017), five sequential propensity score–matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti‐inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase‐2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity‐score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1‐year follow‐up, 518 hip fracture (3.7/1000 person‐years) occurred in the tramadol cohort and 401 (2.9/1000 person‐years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person‐years for tramadol, 1.7/1000 person‐years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person‐years for tramadol, 2.0/1000 person‐years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person‐years for tramadol, 1.8/1000 person‐years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person‐years for tramadol, 1.5/1000 person‐years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population‐based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

Association of tramadol with all-cause mortality, cardiovascular diseases, venous thromboembolism, and hip fractures among patients with osteoarthritis: a population-based study

“…As suggested by a recent meta-analysis on the comparative effectiveness of NSAIDs and opioid use for knee OA, there is no statistically significant difference in pain relief between tramadol and NSAIDs among OA patients [ 13 ]; however, tramadol is associated with more opioid-related adverse effects, for example, nausea, dizziness, constipation, tiredness, headache, vomiting, and drowsiness [ 14 ]. Several studies have compared risks of serious adverse events between tramadol and alternative commonly prescribed analgesics in patients with OA using the Health Improvement Network data that includes 6% of the UK population [ 11 , 15 , 16 ]. These studies showed that tramadol was associated with a significantly higher risk of mortality, myocardial infarction (MI), and hip fractures as compared to commonly prescribed NSAIDs.…”

Increasing Trends in Opioid Use From 2010 to 2018 in the Region of Valencia, Spain: A Real-World, Population-Based Study

“…This pattern of treatment may be emerging as a substitute for non-steroidal anti-inflammatory drugs and strong opioids due to the growing concern about their risks. Whatever the reason, this finding suggests a generalized perception in our setting of tramadol as "opioidlite," with minimal side effects or propensity for addiction and misuse (Stannard, 2019); this perception contrasts with growing evidence of its adverse effects (Fournier et al, 2015;Zeng et al, 2019;Wei et al, 2020) and addictive potential (Thiels et al, 2019). Third, from 2016 the curve of annual opioid treatments started to flatten, mainly due to the slow-down in tramadol and fentanyl prescriptions.…”

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

“…Tapentadol is unique in pharmacologic and pharmacokinetic profiles and can be a valuable option in cases of significant widespread opioid intolerance, but is completely reliant on renal function for excretion. While tramadol is also sometimes considered in patients with intolerance to preferred opioids, its diverse receptor profile confers increased adverse event risks that are especially undesirable in the postoperative period, in addition to previously discussed risks related to its metabolic pathways [417,[420][421][422][423][424][425][426][427][428]. Pharmacists can also assess medication regimens for clinically significant drug-drug pharmacokinetic interactions, especially in patients on antiepileptic medications, azole antifungals, or rifampin [413,429,430].…”