Association between the type of hypnotic drug and in-hospital fractures in older patients with neurocognitive disorders: A case-control study using a nationwide database

Aim: Hypnotics might increase the risk of falls and fractures in older patients with neurocognitive disorders. Orexin receptor antagonists have recently been approved, but the relationship between the new drugs and fractures remains unclarified. This study aimed to evaluate the association between the type of hypnotic and in-hospital fractures in older patients with neurocognitive disorders using a nationwide inpatient database. Methods: Using the Japanese Diagnosis Procedure Combination database, we collected information on inpatients aged >= 65 years with neurocognitive disorders between April 2014 and March 2021. We examined trends in the prescription patterns of benzodiazepine drugs, Z-drugs, orexin receptor antagonists and melatonin receptor agonists. We also carried out a 1:4 matched case-control analysis of in-hospital fractures. The odds ratio of each hypnotic drug was estimated using a generalized estimating equation with adjustment for walking ability, comorbidities, osteoporosis, dialysis, selective serotonin reuptake inhibitor use and antidementia drug use. Results: The prescription of benzodiazepine hypnotics decreased and that of orexin receptor antagonists increased. This case-control analysis included 6832 patients with fractures and 23 463 controls. Ultrashort-acting benzodiazepines, short-acting benzodiazepines and Z-drugs were associated with an increased risk of bone fracture (odds ratio [95% confidence interval] 1.38 [1.08-1.77], 1.38 [1.27-1.50], 1.49 [1.37-1.61], respectively). Orexin receptor antagonists were not associated with an increased risk of bone fracture (1.07 [0.95-1.19]). Conclusions: In contrast to other types of hypnotics, orexin receptor antagonists were not associated with in-hospital fractures in older patients with neurocognitive disorders.