Document Type


Publication Date

Fall 11-13-2019

Publication Title

Concurrent Receipt of Multiple Fracture-Associated Drugs and Hip Fracture


Geisel School of Medicine


Importance: Many prescription drugs increase fracture risk, which raises concern for patients receiving 2 or more such drugs concurrently. Logic suggests that risk will increase with each additional drug, but the risk of taking multiple fracture-associated drugs (FADs) is unknown.

Objective: To estimate hip fracture risk associated with concurrent exposure to multiple FADs.

Design, Setting, and Participants: This cohort study used a 20% random sample of Medicare fee-for-service administrative data for age-eligible Medicare beneficiaries from 2004 to 2014. Sex-stratified Cox regression models estimated hip fracture risk associated with current receipt of 1, 2, or 3 or more of 21 FADs and, separately, risk associated with each FAD and 2-way FAD combination vs no FADs. Models included sociodemographic characteristics, comorbidities, and use of non-FAD medications. Analyses began in November 2018 and were completed April 2019.

Exposure: Receipt of prescription FADs.

Main Outcomes and Measures: Hip fracture hospitalization.

Results: A total of 11.3 million person-years were observed, reflecting 2,646,255 individuals (mean [SD] age, 77.2 [7.3] years, 1,615,613 [61.1%] women, 2,136,585 [80.7%] white, and 219 579 [8.3%] black). Overall, 2,827,284 person-years (25.1%) involved receipt of 1 FAD; 1,322,296 (11.7%), 2 FADs; and 954,506 (8.5%), 3 or more FADs. In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P<.001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P<.001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P<.001). Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P<.001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P<.001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P<.001). Among women, 2 individual FADs were associated with HRs greater than 3.00; 80 pairs of FADs exceeded this threshold. Common, risky pairs among women included sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P<.001), serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P<.001), and proton pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P<.001). Receipt of 1, 2, or 3 or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P<.001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P<.001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P<.001).

Conclusions and Relevance: Among older adults, FADs are commonly used and commonly combined. In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (eg, sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.



Original Citation

Emeny RT, Chang CH, Skinner J, et al. Association of Receiving Multiple, Concurrent Fracture-Associated Drugs With Hip Fracture Risk. JAMA Netw Open. 2019;2(11):e1915348. Published 2019 Nov 1. doi:10.1001/jamanetworkopen.2019.15348

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