Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Quantitative Vertebral Bone Density Seen on Chest CT in Chronic Obstructive Pulmonary Disease Patients: Association with Mortality in the Korean Obstructive Lung Disease Cohort

  • Hye Jeon Hwang (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Sang Min Lee (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Joon Beom Seo (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Ji-Eun Kim (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hye Young Choi (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Namkug Kim (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jae Seung Lee (Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Sei Won Lee (Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yeon-Mok Oh (Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2019.07.22
  • Accepted : 2020.02.04
  • Published : 2020.07.01
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Abstract

Objective: Patients with chronic obstructive pulmonary disease (COPD) are known to be at risk of osteoporosis. The purpose of this study was to evaluate the association between thoracic vertebral bone density measured on chest CT (DThorax) and clinical variables, including survival, in patients with COPD. Materials and Methods: A total of 322 patients with COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. DThorax was measured by averaging the CT values of three consecutive vertebral bodies at the level of the left main coronary artery with a round region of interest as large as possible within the anterior column of each vertebral body using an in-house software. Associations between DThorax and clinical variables, including survival, pulmonary function test (PFT) results, and CT densitometry, were evaluated. Results: The median follow-up time was 7.3 years (range: 0.1-12.4 years). Fifty-six patients (17.4%) died. DThorax differed significantly between the different Global Initiative for Chronic Obstructive Lung Disease stages. DThorax correlated positively with body mass index (BMI), some PFT results, and the six-minute walk distance, and correlated negatively with the emphysema index (EI) (all p < 0.05). In the univariate Cox analysis, older age (hazard ratio [HR], 3.617; 95% confidence interval [CI], 2.119-6.173, p < 0.001), lower BMI (HR, 3.589; 95% CI, 2.122-6.071, p < 0.001), lower forced expiratory volume in one second (FEV1) (HR, 2.975; 95% CI, 1.682-5.262, p < 0.001), lower diffusing capacity of the lung for carbon monoxide corrected with hemoglobin (DLCO) (HR, 4.595; 95% CI, 2.665-7.924, p < 0.001), higher EI (HR, 3.722; 95% CI, 2.192-6.319, p < 0.001), presence of vertebral fractures (HR, 2.062; 95% CI, 1.154-3.683, p = 0.015), and lower DThorax (HR, 2.773; 95% CI, 1.620-4.746, p < 0.001) were significantly associated with all-cause mortality and lung-related mortality. In the multivariate Cox analysis, lower DThorax (HR, 1.957; 95% CI, 1.075-3.563, p = 0.028) along with older age, lower BMI, lower FEV1, and lower DLCO were independent predictors of all-cause mortality. Conclusion: The thoracic vertebral bone density measured on chest CT demonstrated significant associations with the patients' mortality and clinical variables of disease severity in the COPD patients included in KOLD cohort.

Keywords

References

  1. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007;176:532-555 
  2. Lopez AD, Shibuya K, Rao C, Mathers CD, Hansell AL, Held LS, et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J 2006;27:397-412 
  3. Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 2004;364:709-721 
  4. Agusti AGN. Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005;2:367-370; discussion 371-372 
  5. Lehouck A, Boonen S, Decramer M, Janssens W. COPD, bone metabolism, and osteoporosis. Chest 2011;139:648-657 
  6. Graat-Verboom L, van den Borne BE, Smeenk FW, Spruit MA, Wouters EF. Osteoporosis in COPD outpatients based on bone mineral density and vertebral fractures. J Bone Miner Res 2011;26:561-568 
  7. Harrison RA, Siminoski K, Vethanayagam D, Majumdar SR. Osteoporosis-related kyphosis and impairments in pulmonary function: a systematic review. J Bone Miner Res 2007;22:447-457 
  8. Pascual-Guardia S, Badenes-Bonet D, Martin-Ontiyuelo C, Zuccarino F, Marin-Corral J, Rodriguez A, et al. Hospital admissions and mortality in patients with COPD exacerbations and vertebral body compression fractures. Int J Chron Obstruct Pulmon Dis 2017;12:1837-1845 
  9. Lewiecki EM, Gordon CM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, et al. International Society for Clinical Densitometry 2007 adult and pediatric official positions. Bone 2008;43:1115-1121 
  10. Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. Executive summary of the 2013 International Society for Clinical Densitometry position development conference on bone densitometry. J Clin Densitom 2013;16:455-466 
  11. Pickhardt PJ, Lee LJ, del Rio AM, Lauder T, Bruce RJ, Summers RM, et al. Simultaneous screening for osteoporosis at CT colonography: bone mineral density assessment using MDCT attenuation techniques compared with the DXA reference standard. J Bone Miner Res 2011;26:2194-2203 
  12. Pickhardt PJ, Pooler BD, Lauder T, del Rio AM, Bruce RJ, Binkley N. Opportunistic screening for osteoporosis using abdominal computed tomography scans obtained for other indications. Ann Intern Med 2013;158:588-595 
  13. Miyabara Y, Holmes D 3rd, Camp J, Miller VM, Kearns AE. Comparison of calibrated and uncalibrated bone mineral density by CT to DEXA in menopausal women. Climacteric 2012;15:374-381 
  14. Romme EA, Murchison JT, Phang KF, Jansen FH, Rutten EP, Wouters EF, et al. Bone attenuation on routine chest CT correlates with bone mineral density on DXA in patients with COPD. J Bone Miner Res 2012;27:2338-2343 
  15. Biskobing DM. COPD and osteoporosis. Chest 2002;121:609-620 
  16. Jorgensen NR, Schwarz P, Holme I, Henriksen BM, Petersen LJ, Backer V. The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease: a cross sectional study. Respir Med 2007;101:177-185 
  17. Bon J, Fuhrman CR, Weissfeld JL, Duncan SR, Branch RA, Chang CC, et al. Radiographic emphysema predicts low bone mineral density in a tobacco-exposed cohort. Am J Respir Crit Care Med 2011;183:885-890 
  18. Park TS, Lee JS, Seo JB, Hong Y, Yoo JW, Kang BJ, et al. Study design and outcomes of Korean Obstructive Lung Disease (KOLD) cohort study. Tuberc Respir Dis (Seoul) 2014;76:169-174 
  19. Gevenois PA, de Maertelaer V, De Vuyst P, Zanen J, Yernault JC. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med 1995;152:653-657 
  20. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-117 
  21. Crapo RO, Hankinson JL, Irvin C, MacIntyre NR, Voter KZ, Wise RA. American Thoracic Society. Single-breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique--1995 update. Am J Respir Crit Care Med 1995;152:2185-2198 
  22. Bai P, Sun Y, Jin J, Hou J, Li R, Zhang Q, et al. Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis. Respir Res 2011;12:157 
  23. Liang B, Feng Y. The association of low bone mineral density with systemic inflammation in clinically stable COPD. Endocrine 2012;42:190-195 
  24. Budoff MJ, Hamirani YS, Gao YL, Ismaeel H, Flores FR, Child J, et al. Measurement of thoracic bone mineral density with quantitative CT. Radiology 2010;257:434-440 
  25. Budoff MJ, Khairallah W, Li D, Gao YL, Ismaeel H, Flores F, et al. Trabecular bone mineral density measurement using thoracic and lumbar quantitative computed tomography. Acad Radiol 2012;19:179-183 
  26. Mao SS, Li D, Syed YS, Gao Y, Luo Y, Flores F, et al. Thoracic quantitative computed tomography (QCT) can sensitively monitor bone mineral metabolism: comparison of thoracic QCT vs Lumbar QCT and dual-energy X-ray absorptiometry in detection of age-relative change in bone mineral density. Acad Radiol 2017;24:1582-1587 
  27. Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993;8:1137-1148 
  28. Lee YK, Oh YM, Lee JH, Kim EK, Lee JH, Kim N, et al. Quantitative assessment of emphysema, air trapping, and airway thickening on computed tomography. Lung 2008;186:157-165 
  29. Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, et al. Cutoff finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One 2012;7:e51862 
  30. Haruna A, Muro S, Nakano Y, Ohara T, Hoshino Y, Ogawa E, et al. CT scan findings of emphysema predict mortality in COPD. Chest 2010;138:635-640 
  31. Martinez FJ, Foster G, Curtis JL, Criner G, Weinmann G, Fishman A, et al. Predictors of mortality in patients with emphysema and severe airflow obstruction. Am J Respir Crit Care Med 2006;173:1326-1334 
  32. Qu X, Huang X, Jin F, Wang H, Hao Y, Tang T, et al. Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies. Int J Cardiol 2013;166:385-393 
  33. Miller J, Edwards LD, Agusti A, Bakke P, Calverley PM, Celli B, et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med 2013;107:1376-1384 
  34. Campos-Obando N, Castano-Betancourt MC, Oei L, Franco OH, Stricker BH, Brusselle GG, et al. Bone mineral density and chronic lung disease mortality: the Rotterdam study. J Clin Endocrinol Metab 2014;99:1834-1842 
  35. Romme EA, Murchison JT, Edwards LD, van Beek E Jr, Murchison DM, Rutten EP, et al. CT-measured bone attenuation in patients with chronic obstructive pulmonary disease: relation to clinical features and outcomes. J Bone Miner Res 2013;28:1369-1377 
  36. Kung AW, Fan T, Xu L, Xia WB, Park IH, Kim HS, et al. Factors influencing diagnosis and treatment of osteoporosis after a fragility fracture among postmenopausal women in Asian countries: a retrospective study. BMC Womens Health 2013;13:7 
  37. Silva DR, Coelho AC, Dumke A, Valentini JD, de Nunes JN, Stefani CL, et al. Osteoporosis prevalence and associated factors in patients with COPD: a cross-sectional study. Respir Care 2011;56:961-968 
  38. Ohara T, Hirai T, Muro S, Haruna A, Terada K, Kinose D, et al. Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD. Chest 2008;134:1244-1249 
  39. Bon J. Does radiographic emphysema correlate with low bone mineral density? Curr Opin Pulm Med 2012;18:125-130 
  40. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008;19:385-397 
  41. Graat-Verboom L, Spruit MA, van den Borne BE, Smeenk FW, Martens EJ, Lunde R, et al. Correlates of osteoporosis in chronic obstructive pulmonary disease: an underestimated systemic component. Respir Med 2009;103:1143-1151 
  42. Garcia-Rio F, Lores V, Mediano O, Rojo B, Hernanz A, Lopez-Collazo E, et al. Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009;180:506-512 
  43. Nishimura Y, Nakata H, Tsutsumi M, Maeda H, Yokoyama M. Relationship between changes of bone mineral content and twelve-minute walking distance in men with chronic obstructive pulmonary disease: a longitudinal study. Intern Med 1997;36:450-453 
  44. O'Donnell DE. Hyperinflation, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006;3:180-184 
  45. Folgering H, von Herwaarden C. Exercise limitations in patients with pulmonary diseases. Int J Sports Med 1994;15:107-111 
  46. Watz H, Waschki B, Boehme C, Claussen M, Meyer T, Magnussen H. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med 2008;177:743-751 
  47. Loke YK, Cavallazzi R, Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax 2011;66:699-708 
  48. Langhammer A, Forsmo S, Lilleeng S, Johnsen R, Bjermer L. Effect of inhaled corticosteroids on forearm bone mineral density: the HUNT study, Norway. Respir Med 2007;101:1744-1752 
  49. Wise R, Connett J, Weinmann G, Scanlon P, Skeans M; Lung Health Study Research Group. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000;343:1902-1909 
  50. Cummings SR, Lui LY, Eastell R, Allen IE. Association between drug treatments for patients with osteoporosis and overall mortality rates: a meta-analysis. JAMA Intern Med 2019;179:1491-1500