Skip to main content

Advertisement

SpringerLink
Log in

Bone Mineral Density is Associated with Site-Specific Atherosclerosis in Patients with Severe Peripheral Artery Disease

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Recent studies have highlighted a significant association between the severity of atherosclerosis and bone mineral density (BMD) among healthy subjects, although its connection to angiographically determined peripheral artery disease (PAD) has never been investigated. We evaluated the connection between the angiographic severity and site specificity of peripheral atherosclerosis and osteoporosis among patients with chronic lower limb ischemia. In our cross-sectional study we investigated 172 patients with PAD. The anatomic sites of the lesions were analyzed. The severity of atherosclerosis was diagnosed using the Bollinger angiographic score (BS). BMD was measured at the lumbar spine (l-BMD) and at femoral (f-BMD) and radial (r-BMD) sites by dual-energy X-ray absorptiometry. Dyslipidemia, the level of vitamin D3, and different bone turnover markers were also noted. Among PAD patients, regardless of the lesion site, we did not find any association between BMD and BS. Among patients with iliac disease, BS was associated with l-BMD (p = 0.038, r = −0.467) and with f-BMD (p = 0.002, r = −0.642). The level of r-BMD among patients with iliac disease was not associated with BS (p = 0.233, r = −0.306). We did not find any difference between the group of patients with and that without dyslipidemia and low or normal levels of vitamin D3. Our results show a connection between the severity of atherosclerosis and osteoporosis among patients with PAD, specific to the site of the lesion. The findings regarding dyslipidemia, bone markers, and site specificity support the hypothesis that reduced blood flow is the key factor responsible for the inverse association of BMD with atherosclerosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hyder JA, Allison MA, Criqui MH, Wright CM (2007) Association between systemic calcified atherosclerosis and bone density. Calcif Tissue Int 80:301–306

    Article  PubMed  CAS  Google Scholar 

  2. Mangiafico RA, Russo E, Riccobene S, Pennisi P, Mangiafico M, D’Amico F, Fiore CE (2006) Increased prevalence of peripheral arterial disease in osteoporotic postmenopausal women. J Bone Miner Metab 24:125–131

    Article  PubMed  Google Scholar 

  3. von Muhlen D, Allison M, Jassal SK, Barrett-Connor E (2009) Peripheral arterial disease and osteoporosis in older adults: the Rancho Bernardo Study. Osteoporos Int 20:2071–2078

    Article  Google Scholar 

  4. 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 

  5. Laroche M, Pouilles JM, Ribot C, Bendayan P, Bernard J, Boccalon H, Mazieres B (1994) Comparison of the bone mineral content of the lower limbs in men with ischaemic atherosclerotic disease. Clin Rheumatol 13:611–614

    Article  PubMed  CAS  Google Scholar 

  6. Samelson EJ, Cupples LA, Hannan MT, Wilson PW, Williams SA, Vaccarino V, Zhang Y, Kiel DP (2004) Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis Study. Bone 34:557–561

    Article  PubMed  CAS  Google Scholar 

  7. Jensky NE, Hyder JA, Allison MA, Wong N, Aboyans V, Blumenthal RS, Schreiner P, Carr JJ, Wassel CL, Ix JH, Criqui MH (2011) The association of bone density and calcified atherosclerosis is stronger in women without dyslipidemia: the multi-ethnic study of atherosclerosis. J Bone Miner Res 26:2702–2709

    Article  PubMed  CAS  Google Scholar 

  8. Lupattelli G, Scarponi AM, Vaudo G, Siepi D, Roscini AR, Gemelli F, Pirro M, Latini RA, Sinzinger H, Marchesi S, Mannarino E (2004) Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women. Metabolism 53:744–748

    Article  PubMed  CAS  Google Scholar 

  9. Yamaguchi T, Sugimoto T, Yano S, Yamauchi M, Sowa H, Chen Q, Chihara K (2002) Plasma lipids and osteoporosis in postmenopausal women. Endocr J 49:211–217

    Article  PubMed  CAS  Google Scholar 

  10. Parhami F, Morrow AD, Balucan J, Leitinger N, Watson AD, Tintut Y, Berliner JA, Demer LL (1997) Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler Thromb Vasc Biol 17:680–687

    Article  PubMed  CAS  Google Scholar 

  11. Stojanovic OI, Lazovic M, Vuceljic M (2011) Association between atherosclerosis and osteoporosis, the role of vitamin D. Arch Med Sci 7:179–188

    Article  PubMed  Google Scholar 

  12. Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V (2007) Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 158:1–235

    Google Scholar 

  13. Anagnostis P, Athyros VG, Adamidou F, Florentin M, Karagiannis A (2010) Vitamin D and cardiovascular disease: a novel agent for reducing cardiovascular risk? Curr Vasc Pharmacol 8:720–730

    Article  PubMed  CAS  Google Scholar 

  14. Biver E, Chopin F, Coiffier G, Brentano TF, Bouvard B, Garnero P, Cortet B (2012) Bone turnover markers for osteoporotic status assessment? A systematic review of their diagnosis value at baseline in osteoporosis. Joint Bone Spine 79:20–25

    Article  PubMed  Google Scholar 

  15. Chailurkit L, Kruavit A, Rajatanavin R, Ongphiphadhanakul B (2011) The relationship of fetuin-A and lactoferrin with bone mass in elderly women. Osteoporos Int 22:2159–2164

    Article  PubMed  CAS  Google Scholar 

  16. Mori K, Emoto M, Inaba M (2012) Fetuin-A and the cardiovascular system. Adv Clin Chem 56:175–195

    Article  PubMed  CAS  Google Scholar 

  17. Szeberin Z, Fehervari M, Krepuska M, Apor A, Rimely E, Sarkadi H, Szeplaki G, Prohaszka Z, Kalabay L, Acsady G (2011) Serum fetuin-A levels inversely correlate with the severity of arterial calcification in patients with chronic lower extremity atherosclerosis without renal disease. Int Angiol 30:474–475

    PubMed  CAS  Google Scholar 

  18. Ford ML, Tomlinson LA, Smith ER, Rajkumar C, Holt SG (2010) Fetuin-A is an independent determinant of change of aortic stiffness over 1 year in non-diabetic patients with CKD stages 3 and 4. Nephrol Dial Transplant 25:1853–1858

    Article  PubMed  CAS  Google Scholar 

  19. Shioi A, Nishizawa Y (2009) Vascular calcification in chronic kidney disease: pathogenesis and clinical implications. J Ren Nutr 19:78–81

    Article  PubMed  CAS  Google Scholar 

  20. Fodor D, Bondor C, Albu A, Muntean L, Simon SP, Poanta L, Craciun A (2011) Relation between intima-media thickness and bone mineral density in postmenopausal women: a cross-sectional study. Sao Paulo Med J 129:139–145

    PubMed  Google Scholar 

  21. Choi SH, An JH, Lim S, Koo BK, Park SE, Chang HJ, Choi SI, Park YJ, Park KS, Jang HC, Shin CS (2009) Lower bone mineral density is associated with higher coronary calcification and coronary plaque burdens by multidetector row coronary computed tomography in pre- and postmenopausal women. Clin Endocrinol (Oxf) 71:644–651

    Article  Google Scholar 

  22. Beer S, Saely CH, Hoefle G, Rein P, Vonbank A, Breuss J, Gaensbacher B, Muendlein A, Drexel H (2010) Low bone mineral density is not associated with angiographically determined coronary atherosclerosis in men. Osteoporos Int 21:1695–1701

    Article  PubMed  CAS  Google Scholar 

  23. Bollinger A, Breddin K, Hess H, Heystraten FM, Kollath J, Konttila A, Pouliadis G, Marshall M, Mey T, Mietaschk A, Roth FJ, Schoop W (1981) Semiquantitative assessment of lower limb atherosclerosis from routine angiographic images. Atherosclerosis 38:339–346

    Article  PubMed  CAS  Google Scholar 

  24. Natarajan S, Glick H, Criqui M, Horowitz D, Lipsitz SR, Kinosian B (2003) Cholesterol measures to identify and treat individuals at risk for coronary heart disease. Am J Prev Med 25:50–57

    Article  PubMed  Google Scholar 

  25. Holick MF (2000) Calcium and vitamin D. Diagnostics and therapeutics. Clin Lab Med 20:569–590

    PubMed  CAS  Google Scholar 

  26. Maes C, Carmeliet G, Schipani E (2012) Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol 8:358–366

    Article  PubMed  CAS  Google Scholar 

  27. Hung SP, Ho JH, Shih YR, Lo T, Lee OK (2012) Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells. J Orthop Res 30:260–266

    Article  PubMed  Google Scholar 

  28. Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL (2005) Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528

    Article  PubMed  CAS  Google Scholar 

  29. Persy V, D’Haese P (2009) Vascular calcification and bone disease: the calcification paradox. Trends Mol Med 15:405–416

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We warmly thank Rachel Ewings and Daniel Loganathan for English correction, Renáta Dudás for data management, and Edit Máté for the BMD screening.

Author information

Authors and Affiliations

  1. Department of Vascular Surgery, Semmelweis University, 68 Varosmajor Street, Budapest, 1122, Hungary

    Mátyás Fehérvári, Hunor Sarkadi, Miklós Krepuska, Péter Sótonyi, György Acsády, László Entz & Zoltán Szeberin

  2. First Department of Internal Medicine, Semmelweis University, Budapest, Hungary

    Péter Lakatos

Authors
  1. Mátyás Fehérvári
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hunor Sarkadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miklós Krepuska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Péter Sótonyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. György Acsády
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. László Entz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Péter Lakatos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zoltán Szeberin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mátyás Fehérvári.

Additional information

The authors have stated that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fehérvári, M., Sarkadi, H., Krepuska, M. et al. Bone Mineral Density is Associated with Site-Specific Atherosclerosis in Patients with Severe Peripheral Artery Disease. Calcif Tissue Int 93, 55–61 (2013). https://doi.org/10.1007/s00223-013-9727-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-013-9727-5

Keywords

Search

Navigation