Opioid Use and Risk of Nonvertebral Fractures in Adults With Rheumatoid Arthritis: A Nested Case-Control Study Using Administrative Databases

ObjectiveTo assess the risk of nonvertebral fractures in patients with rheumatoid arthritis (RA) who were exposed to opioids. MethodsA population-based, nested case-control study was conducted using health services administrative databases (Quebec, Canada) from 1997 to 2012. Among RA patients, cases of nonvertebral fractures from 2007 to 2012 were identified using a validated algorithm. The date of the first fracture was the index date for the case and his/her matched control. Controls were selected using incidence density sampling and were matched 5:1 to cases for age, sex, and date of RA diagnosis. Opioid exposure was classified as current use, recent past use, remote past use, and nonuse. Conditional logistic regression was used to assess the association of nonvertebral fractures with opioid exposure, adjusting for comorbidity, indicators of RA severity, drugs influencing fracture risk, and health care utilization. ResultsIn total, 1,723 cases and 8,046 controls were identified. Among these patients, 2,595 (722 cases and 1,873 controls) had been exposed to opioids. Current use (versus nonuse) increased the risk of nonvertebral fracture. Cumulative current use of opioids according to the quartile distribution was also associated with the risk of nonvertebral fracture: for continuous use for 1-20 days before the index date, odds ratio (OR) 11.49 (95% confidence interval [95% CI] 8.81-14.99); for 21-155 days, OR 1.75 (95% CI 1.31-2.33); for 156-355 days, OR 1.54 (95% CI 1.17-2.04); and for 356 days, OR 1.73 (95% CI 1.31-2.30). No association between the risk of nonvertebral fractures and recent past use or remote past use of opioids was observed. ConclusionAmong RA patients, the risk of nonvertebral fracture is increased in those treated with opioids.