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

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.

[1]  H. D. de Koning,et al.  Association of Chronic Obstructive Pulmonary Disease and Smoking Status With Bone Density and Vertebral Fractures in Male Lung Cancer Screening Participants , 2014, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[2]  M. Bouxsein,et al.  Bone Loss After Bariatric Surgery: Discordant Results Between DXA and QCT Bone Density , 2014, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  Stephanie A. Santorico,et al.  Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema , 2014, Thorax.

[4]  W. Tan,et al.  A United Kingdom perspective on the relationship between body mass index (BMI) and bone health: a cross sectional analysis of data from the Nottingham Fracture Liaison Service. , 2014, Bone.

[5]  D. Mellström,et al.  High-Sensitivity CRP Is an Independent Risk Factor for All Fractures and Vertebral Fractures in Elderly Men: The MrOS Sweden Study , 2014, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  Carla G. Wilson,et al.  Relationships between airflow obstruction and quantitative CT measurements of emphysema, air trapping, and airways in subjects with and without chronic obstructive pulmonary disease. , 2013, AJR. American journal of roentgenology.

[7]  L. Edwards,et al.  CT‐measured bone attenuation in patients with chronic obstructive pulmonary disease: Relation to clinical features and outcomes , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  A. Looker Femur neck bone mineral density and fracture risk by age, sex, and race or Hispanic origin in older US adults from NHANES III , 2013, Archives of Osteoporosis.

[9]  B. Ettinger,et al.  Performance of FRAX in a cohort of community-dwelling, ambulatory older men: the Osteoporotic Fractures in Men (MrOS) study , 2013, Osteoporosis International.

[10]  Na Li,et al.  Comparison of QCT and DXA: Osteoporosis Detection Rates in Postmenopausal Women , 2013, International journal of endocrinology.

[11]  Edwin K Silverman,et al.  Quantitative Computed Tomography of the Lungs and Airways in Healthy Nonsmoking Adults , 2012, Investigative radiology.

[12]  M. Cooper,et al.  Association between bone mineral density and C-reactive protein in a large population-based sample. , 2012, Arthritis and rheumatism.

[13]  David Gur,et al.  Radiographic emphysema predicts low bone mineral density in a tobacco-exposed cohort. , 2011, American journal of respiratory and critical care medicine.

[14]  J. Jardim,et al.  Association of oxidative stress markers and C-reactive protein with multidimensional indexes in COPD , 2011, Chronic respiratory disease.

[15]  E. Regan,et al.  Genetic Epidemiology of COPD (COPDGene) Study Design , 2011, COPD.

[16]  J. Kaufman,et al.  Early smoking is associated with peak bone mass and prevalent fractures in young, healthy men , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  G. Armbrecht,et al.  High prevalence of vertebral deformities in COPD patients: relationship to disease severity , 2009, European Respiratory Journal.

[18]  A. Spungen,et al.  Dual-energy X-ray absorptiometry overestimates bone mineral density of the lumbar spine in persons with spinal cord injury , 2009, Spinal Cord.

[19]  S. Muro,et al.  Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD. , 2008, Chest.

[20]  P. Shekelle,et al.  Screening for osteoporosis in men: a clinical practice guideline from the American College of Physicians. , 2008, Annals of internal medicine.

[21]  J. Gaughan,et al.  African Americans and Men with Severe COPD Have a High Prevalence of Osteoporosis , 2008, COPD.

[22]  D. Mellström,et al.  Smoking is associated with lower bone mineral density and reduced cortical thickness in young men. , 2007, The Journal of clinical endocrinology and metabolism.

[23]  B. Riggs,et al.  The role of the immune system in the pathophysiology of osteoporosis , 2005, Immunological reviews.

[24]  H. Kroger,et al.  Smoking and fracture risk: a meta-analysis , 2005, Osteoporosis International.

[25]  N. Lane,et al.  Quantitative computed tomography of the lumbar spine, not dual x-ray absorptiometry, is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy. , 2002, Arthritis and rheumatism.

[26]  D. Biskobing COPD and osteoporosis. , 2002, Chest.

[27]  J. Rubin,et al.  Declining bone mass in men with chronic pulmonary disease: contribution of glucocorticoid treatment, body mass index, and gonadal function. , 1999, Chest.

[28]  N. Jørgensen,et al.  The influence of smoking on vitamin D status and calcium metabolism , 1999, European Journal of Clinical Nutrition.

[29]  C. Mcevoy,et al.  Association between corticosteroid use and vertebral fractures in older men with chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[30]  T. Schacker,et al.  Clinical and Epidemiologic Features of Primary HIV Infection , 1996, Annals of Internal Medicine.

[31]  M. Nevitt,et al.  Vertebral fracture assessment using a semiquantitative technique , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  E. Barrett-Connor,et al.  Cigarette smoking and bone mineral density in older men and women. , 1993, American journal of public health.

[33]  E. Orwoll,et al.  The impact of osteophytic and vascular calcifications on vertebral mineral density measurements in men. , 1990, The Journal of clinical endocrinology and metabolism.

[34]  D. House,et al.  Chronic respiratory disease: in military inductees and parents of schoolchildren. , 1973, Archives of environmental health.

[35]  Carol Wilson Bone: Oxidative stress and osteoporosis , 2014, Nature Reviews Endocrinology.

[36]  A. Agustí Global Initiative for Chronic Obstructive Lung Disease , 2013 .

[37]  A. Johnsen Low Bone Density , 2010 .

[38]  Jiaquan Xu,et al.  Deaths: preliminary data for 2008. , 2010, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[39]  D. Pisani,et al.  Male osteoporosis. , 2009, Minerva endocrinologica.

[40]  Gabriele Armbrecht,et al.  Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions. , 2008, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[41]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[42]  D. Sin,et al.  The risk of osteoporosis in Caucasian men and women with obstructive airways disease. , 2003, The American journal of medicine.

[43]  Ali H. Mokdad,et al.  Behavioral risk factor surveillance system. , 1989, Iowa medicine : journal of the Iowa Medical Society.