(B-294) Comparative risk of hip fracture associated with initiation of Z-drugs among patients with and without osteoporosis

Background: Z-drugs (zolpidem, zopiclone, eszopiclone, zaleplon) are used to treat insomnia. Substantial evidence links Z-drugs to increased risk of falls and fractures. Low-dose (≤50 mg) trazodone is commonly used off-label to treat insomnia and is thought to have lower fall risk than Z-drugs, though evidence is sparse. In addition, fracture risk after falls is increased in patients with osteoporosis (OP), but whether the increased risk with Z-drugs is modified by OP status is unknown.

Objectives: To estimate the comparative risk of hospitalization for hip fracture with initiation of Z-drugs vs low-dose trazodone among older adults with and without OP.

Methods: This retrospective cohort study included patients ≥65 years in US Medicare (2014-2019) continuously enrolled ≥365 days prior to newly initiating Z-drugs or low-dose trazodone. The incidence rates (IR) of hip fracture hospitalizations, defined by a validated algorithm (PPV=87.8%), among Z-drugs versus low-dose trazodone were stratified by pre-existing osteoporosis assessed during 365-days before medication initiation. Inverse probability treatment weighted Cox regression using propensity scores was performed to estimate adjusted Hazard ratio (aHR) of hospitalization for hip fracture adjusting for sociodemographic, diagnostic, medication, and healthcare utilization variables.

Results: A cohort of 746,861 patients newly initiated Z-drugs (44.7%) or low-dose trazodone (55.3%). The majority were female, white, had hypertension, with a mean age of 76.8 years. Characteristics were similar between groups, though patients initiating Z-drugs were less likely to have osteoporosis or a nursing home stay.
Among 115,298 patients with OP, 47,336 (41.06%) initiated Z-drugs and 67,962 (58.94%) initiated trazodone. There were 589 hospitalizations for hip fracture with a crude IR of 10.4/1000 person-years (kpy) for Z-drugs and 17.8/kpy for trazodone.
Among 631,563 patients without OP, 286,813 (45.41%) initiated Z-drugs and 344,750 (54.59%) initiated trazodone. There were 1,964 hospitalizations for hip fracture with a crude IR of 6.2/kpy for Z-drugs and 11.1/1000kpy for trazodone.
After weighting, trazodone was associated with lower hip fracture risk [aHR 0.86 (95% CI 0.78-0.94)] compared with Z-drugs. There were no significant differences in hip fracture risk associated with Z-drugs vs trazadone between those with OP [aHR 0.91 (0.74-1.12)] and without OP [aHR 0.84 (0.75-0.93)].

Conclusions: Older adults initiating Z-drugs had an increased risk of hip fracture compared to initiators of low-dose trazodone. Although hip fracture rates were higher in patients with than without OP, we found no evidence that pre-existing OP modifies the comparative risk of Z-drugs vs trazodone.