Incident opioid use and risk of hip fracture among persons with Alzheimer disease: a nationwide matched cohort study.

The objective of this study was to investigate whether incident opioid use is associated with an increased risk of hip fractures among community-dwelling persons with Alzheimer disease (AD) and to assess the association in terms of duration of use and opioid strength. Among community-dwelling persons with AD diagnosed in 2010 to 2011 (N = 23,100), a matched cohort study comparing incident opioid users (N = 4750) with opioid nonusers (N = 4750) was constructed. Matching was based on age, sex, and time since AD diagnosis at opioid initiation. Data on drug use and hip fractures were retrieved from nationwide registers. Incident opioid users were identified with a 1-year washout. Cox proportional hazard models compared the risk of hip fracture between opioid use and nonuse, and were weighted with inverse probability of treatment (IPT), based on a propensity score. Age-adjusted incidence rate of hip fractures was 3.47 (95% confidence interval [CI] 2.62-4.33) during opioid use and 1.94 (95% CI 1.65-2.22) during nonuse. Opioid use was associated with an increased risk of hip fracture (IPT-weighted hazard ratio [HR] 1.96, 95% CI 1.27-3.02). The risk was observed during the first 2 months of use (IPT-weighted HR 2.37, 1.04-5.41) and attenuated after that. The results suggest an increase in the risk of hip fracture by increasing opioid strength; weak opioids IPT-weighted HR 1.75 (0.91-3.35), buprenorphine IPT-weighted HR 2.10 (1.41-3.13), and strong opioids IPT-weighted HR 2.89 (1.32-6.32). Further research is needed to find out whether the risk of injurious falls is avoidable by slow titration of opioid doses in the beginning of treatment.