Effect of Inhaled Glucocorticoids and b 2 Agonists on Vertebral Fracture Risk in COPD Patients: The EOLO Study S. Gonnelli • C. Caffarelli • S. Maggi • G. Guglielmi • P. Siviero • S. Rossi • G. Crepaldi • R. Nuti Received: 8 March 2010 / Accepted: 16 May 2010 / Published online: 22 June 2010 Ó Springer Science+Business Media, LLC 2010 Abstract Although inhaled glucocorticoids (GCs) and b 2 agonists are being more frequently prescribed in the man- agement of chronic obstructive pulmonary disease (COPD), their role in the impairment of bone status and in fracture risk remains controversial. This study aimed to evaluate whether the dose of inhaled GCs and b 2 agonists may independently influence bone status and vertebral fracture risk in COPD patients aged 50 years or over. COPD severity, presence of vertebral fractures on lateral chest X-ray, and bone status by quantitative ultrasound (QUS) at the calcaneus were evaluated. The risk of verte- bral fractures was significantly increased in patients taking the highest daily dose ( [ 1,500 lg) of inhaled GCs (OR = 1.4, CI 1.04–1.89). The highest dose of inhaled GCs was significantly associated with low values of stiff- ness index (OR = 1.74, CI 1.03–2.94). Inhaled b 2 agonists were not associated either with increased risk of vertebral fracture or with reduced values of stiffness. Moreover, the risk of fractures was markedly increased in patients with very severe or severe COPD (OR = 2.05, CI 1.28–3.28, and OR = 1.40, CI 1.06–1.82, respectively). In conclusion, in COPD patients high doses of inhaled GCs, but not b 2 agonists, are associated with an increased risk of vertebral fractures and a reduction of QUS at the calcaneus. Keywords Vertebral fracture Á Inhaled glucocorticoid Á b 2 agonist Á COPD Á QUS Chronic obstructive pulmonary disease (COPD) is, and will increasingly be, a major cause of morbidity and mortality worldwide. In the United States, COPD is the fourth leading cause of death in older adults and, by 2020, it is projected to be the third leading cause of death for both men and women [1]. COPD is now considered a multi- component disease, and attention has focused on the role of comorbidities in determining disease severity in individual patients [2]. Among the comorbidities associated with COPD, osteoporosis is believed to affect 36–60% of patients who are suffering from this chronic lung disease [3–5]. Moreover, several studies have reported that in COPD patients the risk of osteoporosis is related to the severity of COPD [6, 7]. The occurrence of fractures as a consequence of osteoporosis can contribute to disability and mortality of patients with COPD and add to the eco- nomic burden associated with the disease [3, 8, 9]. It is unknown whether osteoporosis in COPD is due to its systemic nature, to physical limitations, or to pharma- cological interventions. One of the most obvious causes of osteoporosis in COPD patients is treatment with gluco- corticoids (GCs), both as systemic therapy and as inhaled GCs [3]. Many studies have reported that oral GCs repre- sent a proven risk factor for osteoporosis and fractures [10]. Moreover, in a comprehensive meta-analysis van Staa et al. [11] found strong correlations between GC cumulative dose and bone loss and between GC daily dose and risk of fracture. Although inhaled GCs are being more frequently The authors have stated that they have no conflict of interest. S. Gonnelli (&) Á C. Caffarelli Á S. Rossi Á R. Nuti Department of Internal Medicine, Endocrine-Metabolic Science, and Biochemistry, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100 Siena, Italy e-mail: gonnelli@unisi.it S. Maggi Á P. Siviero Á G. Crepaldi CNR Aging Branch, University of Padua, Padua, Italy G. Guglielmi Department of Radiology, Scientific Institute Hospital, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy 123 Calcif Tissue Int (2010) 87:137–143 DOI 10.1007/s00223-010-9392-x