Chronic Obstructive Pulmonary Disease and Incidence of Hip Fracture: A Nested Case–Control Study in the EpiChron Cohort

Jesús Díez-Manglano,1,2 María Berges Vidal,2 Lucía Martínez Barredo,3 Beatriz Poblador-Plou,2 Antonio Gimeno-Miguel,2 Pilar Martínez Heras,3 Alexandra Prados-Torres2 1Internal Medicine Department, Royo Villanova Hospital, Zaragoza, Spain; 2EpiChron Research Group, Aragon Health Sciences Institute, IIS Aragón, REDISSEC, Zaragoza, Spain; 3Internal Medicine Department, Miguel Servet University Hospital, Zaragoza, SpainCorrespondence: Jesús Díez-Manglano Duquesa Villahermosa nº 163, 8º D, Zaragoza 50009, SpainTel +34976466910Fax +34976466919Email jdiez@aragon.esPurpose: To determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for hip fracture and identify other factors associated with hip fracture.Patients and Methods: Observational nested case–control study was conducted in Aragon, Spain in 2010. We included COPD patients aged > 40 years, in the EpiChron cohort. Each COPD patient was matched for age, sex, and number of comorbidities with a control subject without COPD. Patients with an existing diagnosis of osteoporosis and those with hip fracture before 2011 were excluded. We collected baseline demographic, comorbidity, and pharmacological treatment data. During a 5-year follow-up period, we recorded the incidence of hip fracture. A logistic regression model was constructed to identify factors associated with hip fracture.Results: The study population consisted of 26,517 COPD patients and the same number of controls (median [interquartile range] age, 74 [17] years; women, 24.7%). Smoking and heart failure were more frequent in COPD patients, and obesity, hypertension, diabetes, dyslipidemia, stroke, arthritis, and visual or hearing impairment were less frequent (all p< 0.001). Consumption of benzodiazepines (p=0.037), bronchodilators (p< 0.001), and corticosteroids (p< 0.001) was higher in the COPD group, while that of beta-blockers and thiazides was lower (both p< 0.001). During follow-up, 898 (1.7%) patients experienced hip fracture, with no differences observed between COPD and control patients. Multivariate analysis revealed that independent of COPD status, age, female sex, chronic liver disease, heart failure, and benzodiazepine use were independently associated with a higher risk of hip fracture, and obesity with a lower risk. In COPD patients, use of inhaled anticholinergics was independently associated with hip fracture (OR, 1.390; 95% CI 1.134– 1.702; p=0.001).Conclusion: COPD is not a risk factor for a hip fracture within 5 years. The association between the use of inhaled anticholinergics and risk of hip fracture warrants further study.Keywords: chronic obstructive pulmonary disease, hip fracture, case–control study, incidence