Although inhaled glucocorticoids (GCs) and beta(2) agonists are being more frequently prescribed in the management 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 beta(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 vertebral fractures was significantly increased in patients taking the highest daily dose (>1,500 microg) of inhaled GCs (OR = 1.4, CI 1.04-1.89). The highest dose of inhaled GCs was significantly associated with low values of stiffness index (OR = 1.74, CI 1.03-2.94). Inhaled beta(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 beta(2) agonists, are associated with an increased risk of vertebral fractures and a reduction of QUS at the calcaneus.