Association between benzodiazepines use and risk of hip fracture in the elderly people: A meta-analysis of observational studies

Objective: Hip fracture is one of the leading causes of disability, cost, morbidity, and mortality. Several studies reported that benzodiazepines (BDZs) have been associated with an increased risk of hip fracture in older individuals. The aim of this study was to evaluate the magnitude of hip fracture risk with BDZs. Methods: A systematic literature search on EMBASE, PubMed, Google Scholar, Scopus was performed between January 1, 1980, and March 31, 2019. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, and an observational study design was mandatory for articles inclusion. Data were extracted by two authors independently and a random effect model was used to evaluate effect size. The random-effects model (DerSimonian-Laird) was utilized to obtain the overall risk ratio (RR) and its 95% CI for all studies. The Newcastle Ottawa Scale (NOS) was also used to assess the quality of each study. Results: Of 2315 studies screened, 33 (20 cohorts and 13 case-control) with 169,660 hip fracture cases were included in our analysis. In BDZs users, compared with non-users, the RR for hip fracture was 1.34 (95%CI: 1.26–1.44). The RR for long- and short-short acting BDZs and hip fracture risk were 1.31 (95%CI: 1.18–1.45, P < 0.0001), and 1.15 (95%CI: 1.08–1.22, P < 0.0001), respectively. When stratified by type of users, the current and recent users of BDZs had higher risk of hip fracture (RR: 1.83, 95% CI: 1.46–2.28, P < 0.0001 and RR: 1.61, 95% 1.30–1.99, P < 0.0001) whereas there was no increased risk of hip fracture in past BDZs users (RR: 1.18, 95%CI: 1.07–1.29, P < 0.0001). Conclusion: Our meta-analysis showed an increased risk of hip fracture in patients with BDZs compared with non-users. Physicians should be aware of the unwanted consequence of BDZs when they will prescribe BDZs for their patients, especially elderly patients because hip fractures are highly prevalent in the elderly population.