Association Between Anticholinergic Drug Exposure and the Risk of Hip Fracture: A Systematic Review and Meta-analysis

Hip fractures are major causes of disability, loss of independence, and mortality in older adults, and anticholinergic drugs (ACs) are commonly prescribed in this population but have been inconsistently linked to hip fracture risk. We conducted a systematic review and meta-analysis to quantify the association between AC exposure and the risk of hip fracture. PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wanfang databases were searched from inception to December 17, 2025. Observational cohort and case-control studies reporting the association between AC exposure and hip fracture were included. Two reviewers independently screened records, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale. Pooled effect estimates were calculated using a random-effects model with Hartung-Knapp adjustment. Six studies met the inclusion criteria. AC exposure was associated with a statistically significant increase in hip fracture risk (odds ratio [OR] = 1.24, 95% confidence interval [CI]: 1.03–1.49), with substantial heterogeneity (I 2 = 87.8%). The direction of effect was consistent in cohort studies (OR = 1.23) and case-control studies, although the latter showed wide confidence intervals. Sensitivity analyses, including leave-one-out analysis and influence diagnostics, supported the robustness of the pooled estimate; however, exclusion of the Drug Burden Index-based study attenuated the association to borderline non-significance (OR = 1.18, 95% CI: 0.98–1.41). Subgroup differences by exposure definition, population type, and study design were not statistically significant. These findings suggest that AC exposure is associated with a modest but significant increase in hip fracture risk among older adults. Clinicians should exercise caution when prescribing ACs to vulnerable older patients, particularly those with high anticholinergic burden or elevated fall risk, and future prospective studies with standardized exposure definitions are needed.