Background Patients with rheumatoid arthritis (RA) are at an increased risk of osteoporosis and fractures.
Objectives To assess whether the use of opioids increases the risk of non-vertebral fractures in RA patients.
Methods A nested case-control study was conducted with Quebec prescription drug, physician billing and hospital discharge data. RA patients aged 20 years and over were identified using International Classification of Disease-9/10 codes (714.x, M05.x, M06.x, M08.x) in billing and hospitalization data. Cases of non-vertebral fracture were identified with an algorithm previously developed and validated. Controls were matched to cases (5:1 ratio) on age, sex, and date of cohort entry. The date of first fracture was defined as index date. Opioids exposure categories were defined as: current use (for individuals with prescription supply that lasted up to or within 30 days the index date), recent past use (31–90 days), remote past use (91–365 days), or nonuse (never use or any use before 365 days). We further classified current use exposure according to the quartile distribution of the days of continuous supply in the year before the index date. Conditional logistic regression was used to calculate odds ratio (OR) and its 95% Confidence Interval (CI), adjusted for comorbidity score, indicators of RA severity (e.g. corticosteroid use, history of arthroplasty), drugs influencing fracture risk, any hospitalization and number of medical visits in the year before the cohort entry.
Results Over the study period, 1,723 cases were identified (8,046 controls), mean age 76.2±11.2 years. The most frequent fracture sites were hip/femur (27.6%), humerus (18.5%), and ankle (12.4%). In total, 2543 patients (674 cases and 1869 controls) were exposed to opioids. Current use of opioids was associated with an increased risk of fracture when compared with nonuse: continuous use in the 1-20 days before the index date (OR=11.49, 95% CI: 8.81-14.99); 21 to 155 days (OR=1.75, 95% CI: 1.31-2.33); 156 to 355 days (OR=1.54, 95% CI: 1.17-2.04) and 356 days or more (OR=1.73, 95% CI: 1.30-2.30). No associations could be confirmed between the recent or remote past use of opioids and the risk of fractures. Other predictors of fracture were comorbidity score, history of osteoporosis, hospitalization, medical visits, hormone replacement therapy, and current use of either antidepressants or acetylsalicylic acid.
Conclusions We found an independent association between current use of opioids and fractures in this population.
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Acknowledgements Brazilian Federal Agency for the Support and Evaluation of Graduate Education (Capes)
Disclosure of Interest None declared