Skip to main content

Advertisement

Log in

Vertebral fractures on routine chest computed tomography: relation with arterial calcifications and future cardiovascular events

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Osteoporosis and cardiovascular disease often coexist. Vertebral fractures incidentally imaged in the course of routine care might be able to contribute to the prediction of cardiovascular events. Following a case-cohort design, 5,679 patients undergoing chest CT were followed for a median duration of 4.4 years. Cases were defined as patients who subsequently developed a cardiovascular event (n = 493). The presence and severity of vertebral fractures, as well as aortic, coronary and valvular calcifications on CT were investigated. Cases were more likely to be male (69 vs 60 %) and older (66 vs 61 years old). Prevalent vertebral fractures conferred an elevated risk of cardiovascular events after adjustment for age and gender [hazard ratio (HR) of 1.28, 95 % confidence interval (CI) 1.07 to 1.54]. This effect remained moderate after correction for cardiovascular calcifications (HR 1.20, CI 0.99–1.44). However, in terms of discrimination, vertebral fractures did not have substantial incremental prognostic value after correction (C-index was 0.683 vs 0.682 for models with and without vertebral fractures respectively). Prevalent vertebral fractures on routine clinical chest CT are related to future cardiovascular events but do not have additional prognostic value to models that already include age, gender and cardiovascular calcifications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Alwan A, World Health Organization (2011) Global status report on noncommunicable diseases 2010. World Health Organization, Geneva

    Google Scholar 

  2. Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367:2010–2018. doi:10.1016/S0140-6736(06)68891-0

    Article  CAS  Google Scholar 

  3. Gondrie MJA, van der Graaf Y, Jacobs PC et al (2011) The association of incidentally detected heart valve calcification with future cardiovascular events. Eur Radiol 21:963–973. doi:10.1007/s00330-010-1995-0

    Article  PubMed Central  PubMed  Google Scholar 

  4. Gondrie MJA, Mali WPTM, Jacobs PC et al (2010) Cardiovascular disease: prediction with ancillary aortic findings on chest CT scans in routine practice. Radiology 257:549–559. doi:10.1148/radiol.10100054

    Article  PubMed  Google Scholar 

  5. Jacobs PC, Gondrie MJ, Mali WP et al (2011) Unrequested information from routine diagnostic chest CT predicts future cardiovascular events. Eur Radiol 21:1577–1585. doi:10.1007/s00330-011-2112-8

    Article  PubMed Central  PubMed  Google Scholar 

  6. Persy V, D’Haese P (2009) Vascular calcification and bone disease: the calcification paradox. Trends Mol Med 15:405–416. doi:10.1016/j.molmed.2009.07.001

    Article  CAS  PubMed  Google Scholar 

  7. Doherty TM, Fitzpatrick LA, Inoue D et al (2004) Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev 25:629–672. doi:10.1210/er.2003-0015

    Article  CAS  PubMed  Google Scholar 

  8. Lampropoulos CE, Papaioannou I, D’Cruz DP (2012) Osteoporosis–a risk factor for cardiovascular disease? Nat Rev Rheumatol 8:587–598. doi:10.1038/nrrheum.2012.120

    Article  CAS  PubMed  Google Scholar 

  9. Enneman AW, Swart KMA, Zillikens MC et al (2014) The association between plasma homocysteine levels and bone quality and bone mineral density parameters in older persons. Bone 63:141–146. doi:10.1016/j.bone.2014.03.002

    Article  CAS  PubMed  Google Scholar 

  10. Zhang H, Tao X, Wu J (2014) Association of homocysteine, vitamin B12, and folate with bone mineral density in postmenopausal women: a meta-analysis. Arch Gynecol Obstet 289:1003–1009. doi:10.1007/s00404-013-3075-6

    Article  CAS  PubMed  Google Scholar 

  11. McLean RR, Jacques PF, Selhub J et al (2008) Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab 93:2206–2212. doi:10.1210/jc.2007-2710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. McLean RR, Jacques PF, Selhub J et al (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042–2049. doi:10.1056/NEJMoa032739

    Article  CAS  PubMed  Google Scholar 

  13. Spence JD (2007) Homocysteine-lowering therapy: a role in stroke prevention? Lancet Neurol 6:830–838. doi:10.1016/S1474-4422(07)70219-3

    Article  CAS  PubMed  Google Scholar 

  14. Spence JD (2013) B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes. Clin Chem Lab Med CCLM FESCC 51:633–637. doi:10.1515/cclm-2012-0465

    CAS  Google Scholar 

  15. Smith WS, Johnston SC, Skalabrin EJ et al (2003) Spinal manipulative therapy is an independent risk factor for vertebral artery dissection. Neurology 60:1424–1428

    Article  CAS  PubMed  Google Scholar 

  16. Beaudry M, Spence JD (2003) Motor vehicle accidents: the most common cause of traumatic vertebrobasilar ischemia. Can J Neurol Sci J Can Sci Neurol 30:320–325

    Article  Google Scholar 

  17. Miley ML, Wellik KE, Wingerchuk DM, Demaerschalk BM (2008) Does cervical manipulative therapy cause vertebral artery dissection and stroke? Neurologist 14:66–73. doi:10.1097/NRL.0b013e318164e53d

    Article  PubMed  Google Scholar 

  18. Krumholz HM, Weintraub WS, Bradford WD et al (2002) Task force #2–the cost of prevention: can we afford it? Can we afford not to do it? 33rd Bethesda Conference. J Am Coll Cardiol 40:603–615

    Article  PubMed  Google Scholar 

  19. Uzzan B, Cohen R, Nicolas P et al (2007) Effects of statins on bone mineral density: a meta-analysis of clinical studies. Bone 40:1581–1587. doi:10.1016/j.bone.2007.02.019

    Article  CAS  PubMed  Google Scholar 

  20. Schoofs MWCJ, Sturkenboom MCJM, van der Klift M et al (2004) HMG-CoA reductase inhibitors and the risk of vertebral fracture. J Bone Miner Res 19:1525–1530. doi:10.1359/JBMR.040607

  21. Santos LL, Cavalcanti TB, Bandeira FA (2012) Vascular effects of bisphosphonates-a systematic review. Clin Med Insights Endocrinol Diabetes 5:47–54. doi:10.4137/CMED.S10007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Smith-Bindman R, Miglioretti DL, Johnson E et al (2012) Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996–2010. JAMA 307:2400–2409. doi:10.1001/jama.2012.5960

    Article  CAS  PubMed  Google Scholar 

  23. Mets OM, de Jong PA, Prokop M (2012) Computed tomographic screening for lung cancer: an opportunity to evaluate other diseases. JAMA 308:1433–1434. doi:10.1001/jama.2012.12656

    Article  CAS  PubMed  Google Scholar 

  24. Bartalena T, Giannelli G, Rinaldi MF et al (2009) Prevalence of thoracolumbar vertebral fractures on multidetector CT: underreporting by radiologists. Eur J Radiol 69:555–559. doi:10.1016/j.ejrad.2007.11.036

    Article  PubMed  Google Scholar 

  25. Woo EK, Mansoubi H, Alyas F (2008) Incidental vertebral fractures on multidetector CT images of the chest: prevalence and recognition. Clin Radiol 63:160–164. doi:10.1016/j.crad.2007.01.031

    Article  CAS  PubMed  Google Scholar 

  26. Williams AL, Al-Busaidi A, Sparrow PJ et al (2009) Under-reporting of osteoporotic vertebral fractures on computed tomography. Eur J Radiol 69:179–183. doi:10.1016/j.ejrad.2007.08.028

    Article  PubMed  Google Scholar 

  27. Müller D, Bauer JS, Zeile M et al (2008) Significance of sagittal reformations in routine thoracic and abdominal multislice CT studies for detecting osteoporotic fractures and other spine abnormalities. Eur Radiol 18:1696–1702. doi:10.1007/s00330-008-0920-2

    Article  PubMed  Google Scholar 

  28. Hasserius R, Karlsson MK, Nilsson BE et al (2003) Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 14:61–68. doi:10.1007/s00198-002-1316-9

    Article  CAS  Google Scholar 

  29. Bandeira E, Neves AP, Costa C, Bandeira F (2012) Association between vascular calcification and osteoporosis in men with type 2 diabetes. J Clin Densitom Off J Int Soc Clin Densitom 15:55–60. doi:10.1016/j.jocd.2011.07.002

    Article  Google Scholar 

  30. Silva HC, Pinheiro MM, Genaro PS et al (2013) Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements. Bone 52:562–567. doi:10.1016/j.bone.2012.11.004

    Article  PubMed  Google Scholar 

  31. Mazziotti G, Baracca M, Doga M et al (2012) Prevalence of thoracic vertebral fractures in hospitalized elderly patients with heart failure. Eur J Endocrinol Eur Fed Endocr Soc 167:865–872. doi:10.1530/EJE-12-0566

    Article  CAS  Google Scholar 

  32. Lai S-W, Liao K-F, Lai H-C et al (2013) Risk of major osteoporotic fracture after cardiovascular disease: a population-based cohort study in Taiwan. J Epidemiol Jpn Epidemiol Assoc 23:109–114

    Article  Google Scholar 

  33. Chung DJ, Choi HJ, Chung Y-S et al (2013) The prevalence and risk factors of vertebral fractures in Korean patients with type 2 diabetes. J Bone Miner Metab 31:161–168. doi:10.1007/s00774-012-0398-5

    Article  PubMed  Google Scholar 

  34. Den Uyl D, Nurmohamed MT, van Tuyl LH et al (2011) (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis. Arthritis Res Ther 13:R5. doi:10.1186/ar3224

    Article  Google Scholar 

  35. Von der Recke P, Hansen MA, Hassager C (1999) The association between low bone mass at the menopause and cardiovascular mortality. Am J Med 106:273–278

    Article  PubMed  Google Scholar 

  36. Schulz E, Arfai K, Liu X et al (2004) Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 89:4246–4253. doi:10.1210/jc.2003-030964

    Article  CAS  PubMed  Google Scholar 

  37. Szulc P, Kiel DP, Delmas PD (2008) Calcifications in the abdominal aorta predict fractures in men: MINOS study. J Bone Miner Res 23:95–102. doi:10.1359/jbmr.070903

  38. Naves M, Rodríguez-García M, Díaz-López JB et al (2008) Progression of vascular calcifications is associated with greater bone loss and increased bone fractures. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 19:1161–1166. doi:10.1007/s00198-007-0539-1

    Article  CAS  Google Scholar 

  39. Gondrie MJA, Mali WPTM, Buckens CFM et al (2010) The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design. Eur J Epidemiol 25:751–758. doi:10.1007/s10654-010-9514-9

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. De Bruin A, Karduan J, Gast F et al (2004) Record linkage of hospital discharge register with population register: experiences at Statistics Netherlands. Stat J UN Econ Comm Eur 1:23–32

    Google Scholar 

  41. World Health Organization (2011) International statistical classification of diseases and related health problems. World Health Organization, Geneva

    Google Scholar 

  42. American Medical Association, Medicode (Firm) (1998) ICD-9-CM: international classification of diseases, 9th revision, clinical modification, volumes 1 and 2, color-coded, illustrated, 1999. American Medical Association, Dover

    Google Scholar 

  43. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148. doi:10.1002/jbmr.5650080915

  44. Buckens CF, de Jong PA, Mol C et al (2013) Intra and Interobserver Reliability and Agreement of Semiquantitative Vertebral Fracture Assessment on Chest Computed Tomography. PLoS ONE 8:e71204. doi:10.1371/journal.pone.0071204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Jacobs PCA, Isgum I, Gondrie MJA et al (2010) Coronary artery calcification scoring in low-dose ungated CT screening for lung cancer: interscan agreement. AJR Am J Roentgenol 194:1244–1249. doi:10.2214/AJR.09.3047

    Article  PubMed  Google Scholar 

  46. Onland-Moret NC, van der A DL, van der Schouw YT, et al. (2007) Analysis of case-cohort data: a comparison of different methods. J Clin Epidemiol 60:350–355. doi:10.1016/j.jclinepi.2006.06.022

  47. Harrell FE Jr, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15:361–387. doi:10.1002/(SICI)1097-0258(19960229)15:4<361:AID-SIM168>3.0.CO;2-4

    Article  PubMed  Google Scholar 

  48. Graubard BI, Korn EL (1993) Hypothesis Testing with Complex Survey Data: the Use of Classical Quadratic Test Statistics with Particular Reference to Regression Problems. J Am Stat Assoc 88:629–641. doi:10.1080/01621459.1993.10476316

    Article  Google Scholar 

  49. Kammerer CM, Dualan AA, Samollow PB et al (2004) Bone mineral density, carotid artery intimal medial thickness, and the vitamin D receptor BsmI polymorphism in Mexican American women. Calcif Tissue Int 75:292–298. doi:10.1007/s00223-004-0215-9

    Article  CAS  PubMed  Google Scholar 

  50. Samelson EJ, Cupples LA, Broe KE et al (2007) Vascular calcification in middle age and long-term risk of hip fracture: the Framingham Study. J Bone Miner Res 22:1449–1454. doi:10.1359/jbmr.070519

  51. Sinnott B, Syed I, Sevrukov A, Barengolts E (2006) Coronary calcification and osteoporosis in men and postmenopausal women are independent processes associated with aging. Calcif Tissue Int 78:195–202. doi:10.1007/s00223-005-0244-z

    Article  CAS  PubMed  Google Scholar 

  52. Mussolino ME, Madans JH, Gillum RF (2003) Bone mineral density and stroke. Stroke J Cereb Circ 34:e20–e22. doi:10.1161/01.STR.0000065826.23815.A5

    Article  Google Scholar 

  53. Parhami F (2003) Possible role of oxidized lipids in osteoporosis: could hyperlipidemia be a risk factor? Prostaglandins Leukot Essent Fatty Acids 68:373–378

    Article  CAS  PubMed  Google Scholar 

  54. Danilevicius CF, Lopes JB, Pereira RMR (2007) Bone metabolism and vascular calcification. Braz J Med Biol Res Rev Bras Pesqui Médicas E Biológicas Soc Bras Biofísica Al 40:435–442

    CAS  Google Scholar 

  55. Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292:490–495. doi:10.1001/jama.292.4.490

    Article  CAS  PubMed  Google Scholar 

  56. Koshiyama H, Ogawa Y, Tanaka K, Tanaka I (2006) The unified hypothesis of interactions among the bone, adipose and vascular systems: “osteo-lipo-vascular interactions”. Med Hypotheses 66:960–963. doi:10.1016/j.mehy.2005.11.024

    Article  PubMed  Google Scholar 

  57. Pickhardt PJ, Pooler BD, Lauder T et al (2013) Opportunistic screening for osteoporosis using abdominal computed tomography scans obtained for other indications. Ann Intern Med 158:588–595. doi:10.7326/0003-4819-158-8-201304160-00003

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The PROVIDI Study Group consists of J. Laméris (Department of Radiology, Academic Medical Center, Amsterdam), C. van Kuijk (Department of Radiology, VU University Medical Center Amsterdam), W. ten Hove (Department of Radiology, Gelre Hospitals, Apeldoorn), M. Oudkerk (Department of Radiology, University Medical Center Groningen), Ay L. Oen (Department of Radiology, Elkerliek Hospital, Helmond), J. Wildberger (Department of Radiology, Academic Hospital Maastricht), J. van Heesewijk (Department of Radiology, St Antonius Hospital, Nieuwegein), W. Mali (Department of Radiology, University Medical Center Utrecht), and Y. van der Graaf (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht). This study was funded by a program Grant from the Netherlands Organization for Scientific Research-Medical Sciences (NWO-MW); Grant 40-00812-98-07-005. The funder had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Substudies from the PROVIDI cohort have been previously published, including substudies using cardiovascular endpoints. These patient groups partly overlap with the current manuscript. The current manuscript includes a different subset of patients from the previous studies and investigates a different set of covariates, most notably vertebral fractures.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Constantinus F. Buckens.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Buckens, C.F., de Jong, P.A., Verkooijen, H.M. et al. Vertebral fractures on routine chest computed tomography: relation with arterial calcifications and future cardiovascular events. Int J Cardiovasc Imaging 31, 437–445 (2015). https://doi.org/10.1007/s10554-014-0567-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-014-0567-9

Keywords

Navigation