Fracture risk increased by concurrent use of central nervous system agents in older people: Nationwide case-crossover study

Abstract

Background: Multiple medication use among older patients is reported to increase fracture risk. But this association is unclear in different subgroups and has not been confirmed by a case-crossover study, which can eliminate measurable and unmeasurable time-invariant confounders.

Objective: To estimate the fragility fracture risk associated with concurrent use of multiple central nervous system (CNS) agents in older patients using a case-crossover design.

Methods: This study targeted almost all patients aged ≥65 years in Japan who incurred fragility fractures from May 2013 to September 2014, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB Japan). Conditional logistic regression analysis estimated the risk of fragility fracture associated with the daily number of CNS agents, including subgroup analyses stratified by sex, age, and fracture location.

Results: For 446,101 patients, the adjusted odds ratios (ORs) of fragility fracture increased almost linearly with number of CNS agents; 0, 0-1, 1-2, 2-3, 3-4, 4-5, and >5: OR reference, 1.21 (95% confidence interval, 1.18-1.23), 1.40 (1.35-1.46), 1.58 (1.49-1.67), 1.89 (1.74-2.05), 1.80 (1.60-2.03), and 1.90 (1.61-2.23; trend p < 0.001), respectively. A similar trend was observed for several subgroups, especially in males and those aged ≥85 years, showing marked linearity.

Conclusions: The increased risk of fragility fracture associated with the use of multiple CNS agents was robust in older people in Japan.

Keywords: Case–crossover; Central nervous system agent; Concurrent use; Elderly; Fracture; Polypharmacy.