Concomitant use of benzodiazepines and opioids and risk of fractures in older adults with chronic non-cancer pain in South Korea, 2011-2015: A nested case-control study

초록

Background: Although benzodiazepines (BZDs) and opioids are each associated with an increased risk of fractures, the level of the risk associated with the combined use of these drugs is uncertain. Objectives: To investigate the relationship between the combined use of BZDs and opioids with the risk of fractures in older patients with chronic non-cancer pain. Methods: In this nested case-control study, we used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2015. Among osteoarthritis or low back pain patients (>64 years), cases were defined as the incident diagnosis of hip, humerus or forearm fracture between 2011 and 2015. For each case, up to four controls were matched using age (within 5 years), sex, and cohort entry date. We categorized BZDs exposure windows as current, recent and past use and defined current BZDs exposure as use within 30 days before index date, recent BZDs exposure as use within 31-90 days before index date and past BZDs exposure as use within 91-365 days before index date. We categorized each exposure to BZDs with and without opioids. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of combined use of BZDs and opioids using conditional logistic regression analysis, adjusting for concomitant diseases and concomitant medications. We also performed subgroup analysis according to age groups, type of fracture, the presence of osteoporosis and an antidepressants prescription. Results: We identified 3,487 cases and 12,350 controls. Among them, 81.8% of cases and 82.0% of controls were female, and mean ages were 75.2 (±6.5) and 74.7 (±6.0) years respectively. The aORs (95% CIs) for current use of BZDs + opioids and BZDs alone were 1.34 (1.15-1.57) and 1.04 (0.91-1.17), each compared to non-use. In subgroup analysis of hip fracture, aORs for current use of BZDs + opioids and only BZDs were 1.55 (1.16-2.06) and 1.04 (0.82-1.33) respectively. The aORs for current use of BZDs + opioids were 1.25 (1.03-1.51) in patients with osteoporosis, and 1.06 (0.89-1.25) in patients without osteoporosis. Finally, the aORs for current and past use of BZDs + opioids in patients had a prescription of antidepressants were each 1.44 (1.21-1.72) and 1.31 (1.05-1.64). There was no association with these outcomes in patients without a record of antidepressants. Conclusions: Concomitant use of BZDs and opioids was associated with an increased risk of fractures in older adults with chronic non-cancer pain.