Smokers with emphysema and small airway disease on computed tomography have lower bone density

Abstract

Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=−1.27, P=0.02 and b=−0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.

Differences in bone density on chest CT according to smoking status in males without chronic obstructive lung disease

“…Male smokers, with or without chronic obstructive pulmonary disease (COPD), had a significant risk of low CTBD and vertebral fractures 8 . CTBD was significantly lower in smokers with emphysema and small airway disease on CT 9 . Lower values of CTBD were also found in current smokers compared to former smokers 10 .…”

“…In many previous studies, CTBD has been shown to be an effective method of demonstrating bone mineral loss and has shown good correlation with DEXA-BMD 1,5,7,9,11–16 . Recently, it was also reported that CTBD reflects bone mineral loss more sensitively than DEXA, although CTBD measures were calibrated using specific formulas 12 .…”

<p>Exploring the Association Between Emphysema Phenotypes and Low Bone Mineral Density in Smokers with and without COPD</p>

“… 35 Interestingly, the fundamental basis of emphysema is loss of lung tissue and recent data from the literature shows that emphysema is often associated with less tissue in other body compartments such as BMI, muscle wasting measured as a lower fat-free mass index (FFMI) 36 , 37 as well as low BMD. 6 , 7 , 10 Likewise, a recent study shows that at baseline, patients with more severe emphysema had lower BMI, lower FFMI and a higher prevalence of self-reported osteoporosis. 38 The results of our study are in accordance with this groundswell of literature and support the hypothesis of tissue wasting associated with those smokers that developed emphysema.…”

“…These findings were later replicated in other studies. 10,11 However, none of these studies have explored the association of different emphysema subtypes (centrilobular, panlobular and paraseptal) and the presence of low BMD. Centrilobular emphysema (CLE) is associated with a higher smoking history, 12,13 a unique systemic chronic inflammation 12 and a protease-antiprotease misbalance, 14 that is also associated with osteoporosis.…”

Radiographic Emphysema, Circulating Bone Biomarkers, and Progressive Bone Mineral Density Loss in Smokers

“…Studies assessing the prevalence of either low BMD using gold standard DXA assessments or osteoporotic fractures in smokers with lung disease rarely include detailed assessments of lung function or radiographic emphysema (4,5). Those cohorts that aim to carefully phenotype smokers through pulmonary function testing and chest CT imaging often do not use gold standard assessments of BMD to define osteopenia or osteoporosis (11,(24)(25)(26), but rather rely on patient-reported osteoporosis or nonstandard BMD assessments. Unlike these studies, we combine gold standard DXA assessments of BMD with detailed physiologic and radiographic data in our longitudinal, albeit smaller, smoking cohort.…”