BACKGROUND: Osteoporosis, the most common extra-pulmonary complication of chronic obstructive pulmonary disease (COPD), may be related to general causes or COPD-specific causes such as low forced expiratory volume in 1 s (FEV1) and hypoxia. A few studies reported that emphysema is an independent risk factor for osteoporosis. However, other workers considered the association to be confounded by low FEV1 and low body mass index (BMI) which cluster with emphysema. AIMS: To study the association between osteoporosis and emphysema in a model that includes these potentially confounding factors. METHODS: We studied prospectively 52 COPD patients with both high resolution computed tomography and carbon monoxide diffusion coefficient as diagnostic markers of emphysema. Dual-energy X-ray absorptiometry was used to measure the bone mass density (BMD) of lumbar vertebrae and neck of the femur. Vertebral fractures were evaluated using the Genant semiquantitative score. Multiple linear regression analysis was used to identify the following independent variables: age, BMI, FEV1% predicted, PaO2, emphysema score, C-reactive protein (CRP), and dyspnea score as related to BMD. P <= 0.05 was considered statistically significant. RESULTS: There was no significant difference in the serum Vitamin D levels, vertebral fracture score, or BMD between the emphysematous and nonemphysematous patients. Multivariate analysis showed that (in a model including age, BMI, FEV1, PaO2, emphysema score, CRP, and dyspnea score) only reduced BMI, FEV1, and PaO2 were independent risk factors for low BMD. CONCLUSIONS: The emphysematous phenotype is not a risk factor for osteoporosis independently of BMI, FEV1, and PaO2.