Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk

Abstract

Rationale: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.

Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.

Methods: Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use.

Measurements and main results: vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures.

Conclusions: Male smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population.

Keywords: COPD; low bone density; quantitative computed tomography; smoking; vertebral fractures.

Figure 1.

Bone density and fractures in the COPDGene cohort. (A) The proportion of subjects with normal bone density, intermediate bone density (T-score_QCT less than −1.0 and greater than −2.5), and low bone density (T-score_QCT less than −2.5) as measured by calibrated quantitative computed tomography (QCT) is shown in relation to the severity of chronic obstructive pulmonary disease (COPD) in the cohort of smokers. Subjects with COPD are shown by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of severity and have higher proportions of subjects with low bone density, particularly in the more severe GOLD Stages 3 and 4 groups. GOLD unclassified subjects appeared to be somewhat resistant to the impact of smoking on bone density, but this group had a higher proportion of African American subjects. (B) At each GOLD stage, subjects with fractures had lower mean volumetric bone density than those without fractures. This was significant in all groups, including the smokers without COPD, except never-smokers, whose number was small (n = 68). (C) As the number of vertebral fractures identified increased, the mean volumetric bone mineral density (vBMD) was found to decrease across the cohort. Although fractures occur as a result of both reduced bone strength and the application of mechanical force, this graph demonstrates a relationship between decreasing BMD and number of vertebral fractures sustained by an individual. A history of a previous fracture is a strong predictor of future fractures and supports the value of screening for bone density so that treatment can be initiated and future fractures prevented. (D) Fractures were more frequent in the midthoracic to lower thoracic region and much less common in the upper thoracic region, possibly due to differences in mechanical loading on the vertebral bodies. Of the 3,317 CT scans analyzed for fractures, the figure shows the number of fractures identified at each vertebral level. There were 2,435 fractures identified in total. T8 had the greatest number of fractures (n = 407), possibly representing the increased mechanical load on the midthoracic vertebrae. Eighty-five percent of the fractures occurred in T6-T12.