Skip to main content

Advertisement

Log in

Relationship of Calcification of Atherosclerotic Plaque and Arterial Stiffness to Bone Mineral Density and Osteoprotegerin in Postmenopausal Women Referred for Osteoporosis Screening

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Arterial calcification leading to increased arterial stiffness, a powerful risk factor for cardiovascular disease, may underlie the association of osteoporosis with cardiovascular disease in postmenopausal women. Osteoprotegerin (OPG), an indirect inhibitor of osteoclastogenesis, may be involved in arterial calcification. We examined relationships between calcification of subclinical atherosclerotic plaque and arterial stiffness with bone mineral density (BMD) and OPG in a group of 54 postmenopausal women referred for routine osteoporosis screening by dual-energy X-ray absorptiometric scanning of the lumbar spine and hip. Presence of calcified and noncalcified plaque in carotid and femoral arteries was examined using ultrasonography. Pulse wave velocity (PWV), a measure of arterial stiffness, was determined by sequential tonometry over the carotid and femoral region. Fifty-nine percent of osteoporotic women had calcified (echogenic) plaque at one or more sites compared with 42% and 20% for women with osteopenia and normal BMD, respectively (P = 0.04). There was a significant negative correlation between PWV and hip BMD (r = −0.35, P = 0.01), which remained significant when age, mean arterial pressure, and serum lipids were taken into account (P = 0.05). No significant relationships were observed between serum concentrations of OPG and lumbar spine or total hip BMD or with the number of arterial sites with calcified or noncalcified plaque. However, there was a strong correlation between OPG and PWV (r = 0.44, P = 0.001), which remained significant when adjusted for age (P = 0.01). These findings suggest that decreased BMD is associated with arterial calcification and stiffening and raise the possibility that OPG is a marker of arterial stiffening, independent of any association with BMD.

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. Braithwaite RS, Col NF, Wong JB (2003) Estimating hip fracture morbidity, mortality and costs. J Am Geriatr Soc 51:364–370

    Article  PubMed  Google Scholar 

  2. Wenger NK (2003) Coronary heart disease: the female heart is vulnerable. Prog Cardiovasc Dis 46:199–229

    Article  PubMed  Google Scholar 

  3. McFarlane SI, Muniyappa R, Shin JJ, Bahtiyar G, Sowers JR (2004) Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Endocrine 23:1–10

    Article  PubMed  CAS  Google Scholar 

  4. Barengolts EI, Berman M, Kukreja SC, Kouznetsova T, Lin C, Chomka EV (1998) Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women. Calcif Tissue Int 62:209–213

    Article  PubMed  CAS  Google Scholar 

  5. Farhat GN, Strotmeyer ES, Newman AB, Sutton-Tyrrell K, Bauer DC, Harris T, Johnson KC, Taaffe DR, Cauley JA, for the Health ABC Study (2006) Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study. Calcif Tissue Int 79:102–111

    Article  PubMed  CAS  Google Scholar 

  6. Farhat GN, Cauley JA, Matthews KA, Newman AB, Johnston J, Mackey R, Edmundowicz D, Sutton-Tyrrell K (2006) Volumetric bone mineral density and vascular calcification in middle-aged women: the study of women’s health across the nation. J Bone Miner Res 21:1839–1846

    Article  PubMed  Google Scholar 

  7. Hirose K-I, Tomiyama H, Okazaki R, Arai T, Koji Y, Zaydun G, Hori S, Yamashina A (2003) Increased pulse wave velocity associated with reduced calcaneal quantitative osteo-sono index: possible relationship between atherosclerosis and osteopenia. J Clin Endocrinol Metab 88:2573–2578

    Article  PubMed  CAS  Google Scholar 

  8. Kado DM, Browner WS, Blackwell T, Gore R, Cummings SR (2000) Rate of bone loss is associated with mortality in older women: a prospective study. J Bone Miner Res 15:1974–1980

    Article  PubMed  CAS  Google Scholar 

  9. Pennisi P, Signorelli SS, Riccobene S, Celotta G, Di Pino L, La Malfa T, Fiore CE (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15:389–395

    Article  PubMed  CAS  Google Scholar 

  10. Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V (2004) Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 89:4246–4253

    Article  PubMed  CAS  Google Scholar 

  11. Tankó LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20

    Article  PubMed  Google Scholar 

  12. Tankó LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA, Cummings SR (2005) Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Miner Res 20:1912–1920

    Article  PubMed  Google Scholar 

  13. Uyama O, Yoshimoto Y, Yamamoto Y, Kawai A (1997) Bone changes and carotid atherosclerosis in postmenopausal women. Stroke 28:1730–1732

    PubMed  CAS  Google Scholar 

  14. 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 

  15. Van der Klift M, Pols HAP, Hak AE, Witteman JCM, Hofman A, de Laet CEDH (2002) Bone mineral density and the risk of peripheral arterial disease: the Rotterdam Study. Calcif Tissue Int 70:443–449

    Article  PubMed  Google Scholar 

  16. Doherty TM, Fitzpatrick LA, Inoue D, Qiao J-H, Fishbein MC, Detrano RC, Shah PK, Rajavashisth TB (2004) Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev 25:629–672

    Article  PubMed  CAS  Google Scholar 

  17. de Leeuw F-E, de Groot JC, Oudkerk M, Witteman JCM, Hofman A, vam Gijn J, Breteler MMB (2000) Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly. Stroke 31:425–429

    PubMed  Google Scholar 

  18. Wilson PW, Kauppila LI, O’Donnell CJ, Kiel DP, Hannan M, Polak JM, Cupples LA (2001) Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality. Circulation 103:1529–1534

    PubMed  CAS  Google Scholar 

  19. 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 

  20. Sumino H, Ichikawa S, Kasama S, Takahashi T, Kumakura H, Takayama Y, Kanda T, Sakamaki T, Kurabayashi M (2006) Elevated arterial stiffness in postmenopausal women with osteoporosis. Maturitas 55:212–218

    Article  PubMed  CAS  Google Scholar 

  21. Bagger YZ, Tankó LB, Alexandersen P, Qin G, Christiansen C, for the Prospective Epidemiological Risk Factors Study Group (2006) Radiographic measure of aortic calcification is a site-specific predictor of bone loss and fracture risk at the hip. J Intern Med 259:598–605

    Article  PubMed  CAS  Google Scholar 

  22. Hak AE, Pols HAP, van Hemert AM, Hofman A, Witteman JCM (2000) Progression of aortic calcification is associated with metacarpal bone loss during menopause. A population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926–1931

    PubMed  CAS  Google Scholar 

  23. Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW (2001) Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham Heart Study. Calcif Tissue Int 68:271–276

    Article  PubMed  CAS  Google Scholar 

  24. Abedin M, Tintut Y, Demer LL (2004) Vascular calcification. Mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 24:1161–1170

    Article  PubMed  CAS  Google Scholar 

  25. Ganesan K, Teklehaimanot S, Tran TH, Asuncion M, Norris K (2005) Relationship of C-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc 97:329–333

    PubMed  Google Scholar 

  26. Hofbauer LC, Shui C, Riggs BL, Dunstan CR, Spelsberg TC, O’Brien T, Khosla S (2001) Effects of immunosuppressants on receptor activator of NF-kappaB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells. Biochem Biophys Res Commun 280:334–339

    Article  PubMed  CAS  Google Scholar 

  27. Parhami F, Farfinkel A, Demer LL (2000) Role of lipids in osteoporosis. Arterioscler Thromb Vasc Biol 20:2346–2348

    PubMed  CAS  Google Scholar 

  28. Price PA, June HH, Buckley JR, Williamson MK (2001) Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol 21:1610–1616

    Article  PubMed  CAS  Google Scholar 

  29. Schoppet M, Preissner KT, Hofbauer LC (2002) RANK ligand and osteoprotegerin—paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 22:549–553

    Article  PubMed  CAS  Google Scholar 

  30. Vattikuti R, Towler DA (2004) Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol Endocrinol Metab 286:E686–E696

    Article  PubMed  CAS  Google Scholar 

  31. Baldini V, Mastropasqua M, Francucci CM, D’Erasmo E (2005) Cardiovascular disease and osteoporosis. J Endocrinol Invest 28(Suppl 10):69–72

    PubMed  CAS  Google Scholar 

  32. Clarkson TB (2007) Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause 14:373–384

    Article  PubMed  Google Scholar 

  33. Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, Kuller LH, Cochrane BB, Hunt JR, Ludlam SE, Pettinger MB, Gass M, Margolis KL, Nathan L, Ockene JK, Prentice RL, Robbins J, Stefanick ML, for the WHI, WHI-CACS Investigators (2007) Estrogen therapy and coronary-artery calcification. N Engl J Med 356:2591–2602

    Article  PubMed  CAS  Google Scholar 

  34. Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, Demer LL (1997) Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96:1755–1760

    PubMed  CAS  Google Scholar 

  35. Doherty TM, Tang W, Dascalos S, Watson KE, Demer LL, Shavelle RM, Detrano RC (1997) Ethnic origin and serum levels of 1α,25-dihydroxyvitamin D3 are independent predictors of coronary calcium mass measured by electron-beam computed tomography. Circulation 96:1477–1481

    PubMed  CAS  Google Scholar 

  36. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268

    Article  PubMed  CAS  Google Scholar 

  37. Abedin M, Omland T, Ueland T, Khera A, Aukrust P, Murphy SA, Jain T, Gruntmanis U, McGuire DK, de Lemos JA (2007) Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study). Am J Cardiol 99:513–518

    Article  PubMed  CAS  Google Scholar 

  38. Kadoglou NPE, Gerasimidis T, Golemati S, Kapelouzou A, Karayannacos PE, Liapis CD (2008) The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability. J Vasc Surg 47:55–62

    Article  PubMed  Google Scholar 

  39. Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly people. J Clin Endocrinol Metab 86:631–637

    Article  PubMed  CAS  Google Scholar 

  40. Safar ME, Henry O, Meaume S (2002) Aortic pulse wave velocity: an independent marker of cardiovascular risk. Am J Geriatr Cardiol 11:295–298

    Article  PubMed  Google Scholar 

  41. Blacher J, Asmar R, Djane S, London GM, Safar ME (1999) Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 33:1111–1117

    PubMed  CAS  Google Scholar 

  42. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM (2001) Arterial calcification, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 38:938–942

    Article  PubMed  CAS  Google Scholar 

  43. World Health Organisation (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical Support Series 843. WHO, Geneva

    Google Scholar 

  44. Baran D, Leahey D, von Stetton E (1995) Clinical evaluation of a foruth generation fan-beam DXA system. J Bone Miner Res 10(Suppl 1):S374

    Google Scholar 

  45. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (1997) Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 96:1432–1437

    PubMed  CAS  Google Scholar 

  46. Mancini GB, Dahlof B, Diez J (2004) Surrogate markers for cardiovascular disease: structural markers. Circulation 109(Suppl 1):IV22–IV30

    PubMed  Google Scholar 

  47. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22

    Article  PubMed  CAS  Google Scholar 

  48. Del Sol AI, Moons KG, Hollander M, Hofman A, Koudstaal PJ, Grobbee DE, Breteler MM, Witteman JC, Bots ML (2001) Is carotid intima-media thickness useful in cardiovascular disease risk assessment? The Rotterdam Study. Stroke 32:1532–1538

    PubMed  Google Scholar 

  49. Stork S, van den Beld AW, von Schacky C, Angermann CE, Lamberts SW, Grobbee DE, Bots ML (2004) Carotid artery plaque burden, stiffness, and mortality risk in elderly men: a prospective, population-based cohort study. Circulation 110:344–348

    Article  PubMed  Google Scholar 

  50. Rumberger JA, Schwartz RS, Simons DB, Sheedy PF 3rd, Edwards WD, Fitzpatrick LA (1994) Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy. Am J Cardiol 73:1169–1173

    Article  PubMed  CAS  Google Scholar 

  51. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, Schwartz RS (1998) Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol 31:126–133

    Article  PubMed  CAS  Google Scholar 

  52. Wexler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddahi J, Rumberger J, Stanford W, White R, Taubert K (1996) Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation 94:1175–1192

    PubMed  CAS  Google Scholar 

  53. Jørgensen L, Joakimsen O, Berntsen GKR, Heuch I, Jacobsen BK (2004) Low bone mineral density is related to echogenic carotid artery plaques: a population-based study. Am J Epidemiol 160:549–556

    Article  PubMed  Google Scholar 

  54. Banks LM, Lees B, MacSweeney JE, Stevenson JC (1994) Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? Eur J Clin Invest 24:813–817

    Article  PubMed  CAS  Google Scholar 

  55. Yatura S, Bridges JF, Bryant BA (2005) Calcification of abdominal aorta and osteoporosis. J Bone Miner Res 20(Suppl 1):s158

    Google Scholar 

  56. Schousboe JT, Wilson KE, Kiel DP (2006) Detection of abdominal calcification with lateral spine imaging using DXA. J Clin Densitom 9:302–308

    Article  PubMed  Google Scholar 

  57. Schousboe JT, Taylor BC, Kiel DP, Ensrud KE, Wilson KE, McCloskey EV (2007) Abdominal aortic calcification detected on lateral spine images from a bone densitometer predicts incident myocardial infarction or stroke in older women. J Bone Miner Res 23:409–416

    Article  Google Scholar 

  58. Jayalath RW, Mangan SH, Golledge J (2005) Aortic calcification. Eur J Vasc Endovasc Surg 30:476–488

    Article  PubMed  CAS  Google Scholar 

  59. Sumino H, Ichikawa S, Kasama S, Takahashi T, Sakamoto H, Kumakura H, Takayama Y, Kanda T, Murakami M, Kurabayashi M (2007) Relationship between brachial arterial endothelial function and lumbar spine bone mineral density in postmenopausal women. Circ J 71:1555–1559

    Article  PubMed  CAS  Google Scholar 

  60. Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, Spronk HM, Vermeer C, Daemen DJ (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21:1998–2003

    Article  PubMed  CAS  Google Scholar 

  61. Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14:518–527

    Article  PubMed  CAS  Google Scholar 

  62. Dai Y, Shen L (2007) Relationships between serum osteoprotegerin, matrix metalloproteinase-2 levels and bone metabolism in postmenopausal women. Chin Med J (Engl) 120:2017–2021

    CAS  Google Scholar 

  63. Hofbauer LC, Schoppet M (2002) Osteoprotegerin: a link between osteoporosis and arterial calcification? Lancet 358:257–258

    Article  Google Scholar 

  64. Schoppet M, Schaefer JR, Hofbauer LC (2003) Low serum levels of soluble RANK ligand are associated with the presence of coronary artery disease in men. Circulation 107:76

    Article  Google Scholar 

  65. Kiechl S, Schett G, Schwaiger J, Seppi K, Eder P, Egger G, Santer P, Mayr A, Xu Q, Willeit J (2007) Soluble receptor activator of nuclear factor-kappa B ligand and risk for cardiovascular disease. Circulation 116:385–391

    Article  PubMed  CAS  Google Scholar 

  66. Indridason OS, Franzson L, Sigurdsson G (2005) Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover. Osteoporos Int 16:417–423

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michelle L. Frost.

Additional information

This work was presented in part as an abstract at the National Osteoporosis Society’s 11th Conference on Osteoporosis, Harrogate, UK, June 25–28, 2006.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frost, M.L., Grella, R., Millasseau, S.C. et al. Relationship of Calcification of Atherosclerotic Plaque and Arterial Stiffness to Bone Mineral Density and Osteoprotegerin in Postmenopausal Women Referred for Osteoporosis Screening. Calcif Tissue Int 83, 112–120 (2008). https://doi.org/10.1007/s00223-008-9153-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9153-2

Keywords

Navigation