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COPD as an independent risk factor for osteoporosis and fractures

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Fractures are common in individuals with COPD and occur at higher bone mass values than expected. COPD appears to be an important risk factor for bone fragility.


Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis and fractures, but screening and prophylactic measures to prevent both disorders are often neglected in this population. This case-control study assessed the prevalence of osteopenia, osteoporosis, and fractures in patients with COPD, and identified potential risk factors for fractures in this population.


Overall, 91 patients with COPD (COPD group; COPDG) and 81 age- and sex-matched controls (control group; CG) were assessed with bone mineral density (BMD), thoracic/lumbar spine radiographs, and serum PTH and 25-hydroxyvitamin D (25[OH]D) levels. The occurrence of prior fractures was retrieved from clinical history.


The prevalence of total fractures in the COPDG was 57.1% (odds of fracture 4.7 times greater compared with the CG), and the femoral neck T-score emerged as the best predictor of fractures. Compared with the CG, the COPDG had lower spine and femoral BMD (p ≤ 0.01) and 25(OH)D levels (p = 0.01) and 2.6 times greater odds of osteoporosis. Among men, vertebral fractures were more prevalent in the COPDG versus CG (25.9% vs. 6.5%, respectively, p = 0.01). The odds of fracture increased with femoral neck T-scores ≤ − 2.7 in the CG and ≤ − 0.6 in the COPDG.


These results add robust evidence to an increased odds of osteoporosis and fractures in COPD. Fractures in the COPDG occurred at higher BMD values than expected, suggesting that COPD may be an independent marker of fracture risk, reinforcing a need for regular osteoporosis screening with BMD measurement and prophylaxis of fractures in patients with this disorder.

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  1. Global Initiative for Chronic Obstructive Lung Disease - GOLD. Accessed April 11, 2019

  2. Agusti A (2007) Systemic effects of chronic obstructive pulmonary disease: what we know and what we don’t know (but should). Proc Am Thorac Soc 4(7):522–525.

    Article  PubMed  Google Scholar 

  3. Bon J, Fuhrman CR, Weissfeld JL, Duncan SR, Branch RA, Chang CC, Zhang Y, Leader JK, Gur D, Greenspan SL, Sciurba FC (2011) Radiographic emphysema predicts low bone mineral density in a tobacco-exposed cohort. Am J Respir Crit Care Med 183(7):885–890.

    Article  PubMed  Google Scholar 

  4. Gazzotti MR, Roco CM, Pradella CO, Nascimento OA, Porto EF, Adas M, Lazaretti-Castro M, Jardim JR (2019) Frequency of osteoporosis and vertebral fractures in chronic obstructive pulmonary disease (COPD) patients. Arch Bronconeumol 55(5):252–257.

    Article  PubMed  Google Scholar 

  5. Okazaki R, Watanabe R, Inoue D (2016) Osteoporosis associated with chronic obstructive pulmonary disease. J Bone Metab 23(3):111–120.

    Article  PubMed  PubMed Central  Google Scholar 

  6. de Luise C, Brimacombe M, Pedersen L, Sorensen HT (2008) Chronic obstructive pulmonary disease and mortality following hip fracture: a population-based cohort study. Eur J Epidemiol 23(2):115–122.

    Article  PubMed  Google Scholar 

  7. Morden NE, Sullivan SD, Bartle B, Lee TA (2011) Skeletal health in men with chronic lung disease: rates of testing, treatment, and fractures. Osteoporos Int 22(6):1855–1862.

    Article  CAS  PubMed  Google Scholar 

  8. Ferguson GT, Calverley PMA, Anderson JA, Jenkins CR, Jones PW, Willits LR, Yates JC, Vestbo J, Celli B (2009) Prevalence and progression of osteoporosis in patients with COPD: results from the towards a revolution in COPD health study. Chest 136(6):1456–1465.

    Article  PubMed  Google Scholar 

  9. Densitometry TISfC Offi cial Positions (2015) ISCD Combined - Official Positions of the International Society for Clinical Densitometry. Accessed May 16, 2019

  10. NIH Consensus Development Panel on Osteoporosis Prevention D, Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285(6):785–795

    Article  Google Scholar 

  11. Kelly TL, Wilson KE, Heymsfield SB (2009) Dual energy X-Ray absorptiometry body composition reference values from NHANES. PLoS One 4(9):e7038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Standardization of Spirometry (1994) Update. American Thoracic Society (1995). Am J Respir Crit Care Med 152(3):1107–1136.

    Article  Google Scholar 

  13. Genant HK, Engelke K, Fuerst T, Gluer CC, Grampp S, Harris ST, Jergas M, Lang T, Lu Y, Majumdar S, Mathur A, Takada M (1996) Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res 11(6):707–730.

    Article  CAS  PubMed  Google Scholar 

  14. R: The R Project for Statistical Computing. Accessed September 4, 2017

  15. Biskobing DM (2002) COPD and osteoporosis. Chest 121(2):609–620.

    Article  PubMed  Google Scholar 

  16. Penrod JD, Litke A, Hawkes WG, Magaziner J, Doucette JT, Koval KJ, Silberzweig SB, Egol KA, Siu AL (2008) The association of race, gender, and comorbidity with mortality and function after hip fracture. J Gerontol A Biol Sci Med Sci 63(8):867–872.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rycroft CE, Heyes A, Lanza L, Becker K (2012) Epidemiology of chronic obstructive pulmonary disease: a literature review. Int J Chron Obstruct Pulmon Dis 7:457–494.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Civitelli R, Armamento-Villareal R, Napoli N (2009) Bone turnover markers: understanding their value in clinical trials and clinical practice. Osteoporos Int 20(6):843–851.

    Article  CAS  PubMed  Google Scholar 

  19. Siris ES, Chen YT, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE, Berger ML (2004) Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 164(10):1108–1112.

    Article  PubMed  Google Scholar 

  20. Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B (2001) Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 12(12):989–995.

    Article  CAS  PubMed  Google Scholar 

  21. McCloskey EV, Harvey NC, Johansson H, Kanis JA (2016) FRAX updates 2016. Curr Opin Rheumatol 28(4):433–441.

    Article  PubMed  Google Scholar 

  22. Marques A, Ferreira RJ, Santos E, Loza E, Carmona L, da Silva JA (2015) The accuracy of osteoporotic fracture risk prediction tools: a systematic review and meta-analysis. Ann Rheum Dis 74(11):1958–1967.

    Article  PubMed  Google Scholar 

  23. Kurra S, Fink DA, Siris ES (2014) Osteoporosis-associated fracture and diabetes. Endocrinol Metab Clin N Am 43(1):233–243.

    Article  Google Scholar 

  24. Nayak S, Edwards DL, Saleh AA, Greenspan SL (2014) Performance of risk assessment instruments for predicting osteoporotic fracture risk: a systematic review. Osteoporos Int 25(1):23–49.

    Article  CAS  PubMed  Google Scholar 

  25. Dennison EM, Compston JE, Flahive J, Siris ES, Gehlbach SH, Adachi JD, Boonen S, Chapurlat R, Diez-Perez A, Anderson FA Jr, Hooven FH, LaCroix AZ, Lindsay R, Netelenbos JC, Pfeilschifter J, Rossini M, Roux C, Saag KG, Sambrook P, Silverman S, Watts NB, Greenspan SL, Premaor M, Cooper C, Investigators G (2012) Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone 50(6):1288–1293.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kulak CA, Borba VC, Jorgetti V, Dos Reis LM, Liu XS, Kimmel DB, Kulak J Jr, Rabelo LM, Zhou H, Guo XE, Bilezikian JP, Boguszewski CL, Dempster DW (2010) Skeletal microstructural abnormalities in postmenopausal women with chronic obstructive pulmonary disease. J Bone Miner Res 25(9):1931–1940.

    Article  PubMed  Google Scholar 

  27. Fujimoto H, Fujimoto K, Ueda A, Ohata M (1999) Hypoxemia is a risk factor for bone mass loss. J Bone Miner Metab 17(3):211–216

    Article  CAS  Google Scholar 

  28. Wan C, Shao J, Gilbert SR, Riddle RC, Long F, Johnson RS, Schipani E, Clemens TL (2010) Role of HIF-1alpha in skeletal development. Ann N Y Acad Sci 1192:322–326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LRG, Mewburn JD, Parlow JL, Archer SL (2017) Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest 151(1):181–192.

    Article  PubMed  Google Scholar 

  30. Chen D, Li Y, Zhou Z, Wu C, Xing Y, Zou X, Tian W, Zhang C (2013) HIF-1alpha inhibits Wnt signaling pathway by activating Sost expression in osteoblasts. PLoS One 8(6):e65940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Park JH, Park BH, Kim HK, Park TS, Baek HS (2002) Hypoxia decreases Runx2/Cbfa1 expression in human osteoblast-like cells. Mol Cell Endocrinol 192(1–2):197–203

    Article  CAS  Google Scholar 

  32. Sapey E, Ahmad A, Bayley D, Newbold P, Snell N, Rugman P, Stockley RA (2009) Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD. J Clin Immunol 29(4):508–516.

    Article  CAS  PubMed  Google Scholar 

  33. Takabatake N, Nakamura H, Abe S, Inoue S, Hino T, Saito H, Yuki H, Kato S, Tomoike H (2000) The relationship between chronic hypoxemia and activation of the tumor necrosis factor-alpha system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 161(4 Pt 1):1179–1184.

    Article  CAS  PubMed  Google Scholar 

  34. Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J, Committee E-SS (2010) Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. Respir Res 11:63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bai P, Sun Y, Jin J, Hou J, Li R, Zhang Q, Wang Y (2011) Disturbance of the OPG/RANK/RANKL pathway and systemic inflammation in COPD patients with emphysema and osteoporosis. Respir Res 12:157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mathyssen C, Gayan-Ramirez G, Bouillon R, Janssens W (2017) Vitamin D supplementation in respiratory diseases: evidence from randomized controlled trials. Pol Arch Intern Med 127(11):775–784.

    Article  PubMed  Google Scholar 

  37. Kokturk N, Baha A, Oh YM, Young Ju J, Jones PW (2018) Vitamin D deficiency: what does it mean for chronic obstructive pulmonary disease (COPD)? A compherensive review for pulmonologists. Clin Respir J 12(2):382–397.

    Article  CAS  PubMed  Google Scholar 

  38. Nolasco R, Moreira LDF, Bocalin DS, Fronza FCAO, Marin RV, Lazaretti-Castro M (2017) Effects of vitamin D supplementation on pulmonary function in postmenopausal women following an aquatic exercise program. Arch Endocrinol Metab 2017:61/1.

    Article  Google Scholar 

  39. Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, Chen B, Wang C, Ni D, Zhou Y, Liu S, Wang X, Wang D, Lu J, Zheng J, Ran P (2007) Prevalence of chronic obstructive pulmonary disease in China: a large, population-based survey. Am J Respir Crit Care Med 176(8):753–760.

    Article  PubMed  Google Scholar 

  40. Costa TM, Costa FM, Moreira CA, Rabelo LM, Boguszewski CL, Borba VZ (2015) Sarcopenia in COPD: relationship with COPD severity and prognosis. J Bras Pneumol 41(5):415–421.

    Article  PubMed  PubMed Central  Google Scholar 

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We would like to thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the financial support of the authors M.G.A.O. and M.R.G. and the laboratory tests, and to Roche Diagnostica Brasil for providing the kits for the measurement of bone metabolic markers. We also thank Milena Braga-Basaria (Voxmed Medical Communications) for critically reviewing and suggesting improvements to the manuscript.

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Correspondence to M.G. Adas-Okuma.

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Adas-Okuma, M., Maeda, S., Gazzotti, M. et al. COPD as an independent risk factor for osteoporosis and fractures. Osteoporos Int 31, 687–697 (2020).

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