((SLB-042)) (SLB-042) Association Between Gabapentinoid Use, Concurrent Opioid or Benzodiazepine Therapy, and Traumatic Fracture Risk in Older Adults: A Self-controlled Case Series and Case-Case-Time-Control Study

Background: This study fills a knowledge gap by examining traumatic fracture risk throughout the treatment period of gabapentinoid, addressing methodological challenges of its intermittent use, especially among older adults.

Objectives: To investigate the association between gabapentinoid, including concurrent use with opioids or/ and benzodiazepines, and the incidence of traumatic fractures among individuals aged 60 and above.

Methods: This study utilized data from the UK Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics and Office for National Statistics. Individuals aged 60 years or older who received at least one gabapentinoid prescription and had one hospitalization record of an incident traumatic fracture between 2010 and 2020 were included. Self-controlled case series (SCCS) and case-case-time-control (CCTC) designs were deployed. In the SCCS study, we compared incidence rates during gabapentinoid treatment periods to unexposed baseline periods using conditional Poisson regression, adjusted for age, season and concomitant medications, and calculated incidence rate ratios. A 90-day pre-treatment window was included to address confounding by indication. In the CCTC study, the hazard period was defined as the 30 days preceding the event, and a 30-day reference period was randomly selected from −61 to −180 days before the event. Future cases were selected from patients whose event dates were within 180–360 days after the matched event dates of the current cases. Adjusted odds ratios (OR) were estimated using conditional logistic regression to corroborate the SCCS findings.

Results: 20,030 individuals were included in the SCCS analysis. Of these, 15,366 (76.7%) were female; the mean (SD) age at event was 77.85 (9.07) years. The risk of traumatic fracture was elevated during the 90-day period before treatment initiation (IRR 2.17, 95% CI, 2.06–2.29). This risk decreased to 1.45 (95% CI, 1.34–1.55) during the first 60 days of treatment and further subsided to 1.02 (95% CI, 0.97–1.08) for the remainder of the treatment period. Concurrent use with opioids or benzodiazepines further increased the risk of traumatic fracture. The CCTC study detects elevated odds (OR 1.30, 95% CI, 1.10–1.55) of receiving gabapentinoid treatment shortly before traumatic fracture event.

Conclusions: The risk of traumatic fracture was highest immediately before gabapentinoid treatment initiation and decreased gradually after starting therapy, returning to baseline levels during the treatment period. The elevated pre-treatment risk may reflect worsening underlying conditions coinciding with gabapentinoid prescription. The results do not support a causal association between gabapentinoids and traumatic fractures.