Medications as a Risk Factor for Fragility Hip Fractures: A Systematic Review and Meta-analysis

Fragility hip fractures and their associated morbidity and mortality pose a global healthcare problem. Several pharmaceutical products have been postulated to alter bone architecture and contribute to fragility hip fractures. We searched four electronic databases from inception to September 2017. Inclusion criteria were the following: (1) adult patients with fragility hip fractures, (2) full text in English, (3) minimum one-year follow-up, and (4) reporting of at least one risk factor. To minimize heterogeneity among the studies, we performed subgroup analyses. Whenever heterogeneity remained significant, we employed random effect meta-analysis for data pooling. Thirty-eight studies were included, containing 1,244,155 subjects and 188,966 cases of fragility hip fractures. Following medications were significantly associated with fragility hip fractures: Antidepressants (OR 2.07, 95% CI 1.98-2.17), antiparkinsonian drugs (OR 2.21, 95% CI 1.15-4.24), antipsychotic drugs (OR 2.0, 95% CI 1.50-2.66), anxiolytic drugs (OR 1.44, 95% CI 1.19-1.75), benzodiazepines (OR 1.84, 95% CI 1.26-2.69), sedatives (OR 1.33, 95% CI 1.14-1.54), systemic corticosteroids (OR 1.65, 95% CI 1.37-1.99), H₂ antagonists (OR 1.21, 95% CI 1.18-1.24), proton pump inhibitors (OR 1.41, 95% CI 1.16-1.71), and thyroid hormone (OR 1.29, 95% CI 1.13-1.47). Hormone replacement therapy with estrogen (HRT) was associated with decreased risk of hip fracture (OR 0.80, 95% CI 0.65-0.98). There are several medications associated with sustaining a fragility hip fracture. Medical interventions should be considered for patients on these medications, including information about osteoporosis and fracture prevention.