The effect of inhaled glucocorticoids and beta-adrenergic agonists on bone status in COPD patients inhaled

Among the comorbidities associated with chronic obstructive pulmonary disease (COPD), osteoporosis is elieved to affect 36% to 60% of patients who are suffering from this chronic lung disease. Although inhaled glucocorticoids (GCs) are being more frequently prescribed in the managements of COPD, their role in the reduction of bone mineral density (BMD) and in fracture risk still remains controversial. Also inhaled β-adrenergic agonists have been associated with an increased fracture risk. The EOLO (Evaluation of Obstructive Lung disease and Osteoporosis) study enrolled a total of 3,030 ambulatory COPD patients (1,778 men and 1,262 women) aged 50 years or over. Of COPD patients, 68.3% were treated with GCs (55.0% inhaled GCs, 3.9% oral GCs and 9.5% oral+ inhaled GCs) 16.8% were not treated with specific COPD medications and the remaining 14.7% were treated with short-or long-acting β2-agonists, xanthines or antimuscarinics but not with GCs. The COPD patients treated with inhaled GCs (n=1653) were divided in to 3 groups on the basis of the daily dose of inhaled GCs expressed as beclometasone equivalents: ≤750 μg; 750 – 1500 μg; ≥1500 μg. Betaagonists (long-acting and short-acting) was expressed as albuterol equivalents. In all we carried out spirometry. Moreover, we measured ultrasound parameters at calcaneus: speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness, by Achilles (GE, Lunar); the patientswere divided in to three groups: lowrisk of having osteoporosis (Stiffness ≥78%), high risk of having osteoporosis (Stiffness <57%) and moderate risk of having osteoporosis (Stiffness 57-77%). Themeanvalue of Stiffness (S) was lower in inhaled GCs patients (S=75%) than in COPD patients on no treatment or other treatment (S=78.8% and S=76.2%, respectively) (p=0.006). Logistic regression analysis showed that both COPD severity and inhaled GCs therapy (daily dose ≥1500 μg) were associated to a Stiffness values lower than 57% (OR=3.1, 95% CI 1.51-6.36; OR=1.47, 95% CI 0.92-2.33 and OR=1.60 95% CI 1.10-2.53 for very severe COPD, severe COPD and inhaled GCs≥1500 μg, respectively). These associations remained significant ever after adjustment for inhaled β-adrenergic agonists that did not enter in to the model. In conclusion, in COPD patients the highest doses of inhaled GCs, but not inhaled β-adrenergic agonists, are associatedwith reduced values of Stiffness and represent an important risk for fragility fractures.