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Mechanisms linking osteoporosis with cardiovascular calcification

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Abstract

Cardiovascular calcium deposition is associated with osteoporosis through various potential mechanisms involving molecular regulatory factors at the nanoscale level that govern skeletal bone and cardiovascular tissues. In this article, several possible mechanisms linking cardiovascular calcification and osteoporosis are discussed, including aging, tissue-specific responses to chronic inflammation, flow-limiting atherosclerosis of skeletal end arteries causing ischemic abnormalities in metabolism, shared endogenous regulatory factors that affect the two tissues in a reciprocal manner, and changes in a cysteine protease inhibitor, fetuin. Any or all of these factors and phenomena may contribute to the association.

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References and Recommended Reading

  1. Towler DA: Vascular calcification in ESRD: another cloud appears in the perfect storm—but highlights a silver lining? Kidney Int 2004, 66:2467–2468.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Schousboe JT, Taylor BC, Kiel DP, et al.: 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 2008, 23:409–416.

    Article  PubMed  Google Scholar 

  4. Guzman RJ: Clinical, cellular, and molecular aspects of arterial calcification. J Vasc Surg 2007, 45:A57–A63.

    Article  PubMed  Google Scholar 

  5. Huang H, Virmani R, Younis H, et al.: The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001, 103:1051–1056.

    PubMed  CAS  Google Scholar 

  6. Bluestein D, Alemu Y, Avrahami I, et al.: Influence of microcalcifications on vulnerable plaque mechanics using FSI modeling. J Biomech 2008, 41:1111–1118.

    Article  PubMed  Google Scholar 

  7. Lin TC, Tintut Y, Lyman A, et al.: Mechanical response of a calcified plaque model to fluid shear force. Ann Biomed Eng 2006, 34:1535–1541.

    Article  PubMed  Google Scholar 

  8. Chen NX, O’Neill KD, Chen X, Moe SM: Annexin-mediated matrix vesicle calcification in vascular smooth muscle cells. J Bone Miner Res 2008, 23:1798–1805.

    Article  PubMed  CAS  Google Scholar 

  9. Duer MJ, Friscic T, Proudfoot D, et al.: Mineral surface in calcified plaque is like that of bone: further evidence for regulated mineralization. Arterioscler Thromb Vasc Biol 2008, 28:2030–2034.

    Article  PubMed  CAS  Google Scholar 

  10. Toussaint ND, Lau KK, Strauss BJ, et al.: Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 2008, 23:586–593.

    Article  PubMed  Google Scholar 

  11. Bagger YZ, Tanko LB, Alexandersen P, et al.: Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip. J Intern Med 2006, 259:598–605.

    Article  PubMed  CAS  Google Scholar 

  12. Tekin GO, Kekilli E, Yagmur J, et al.: Evaluation of cardiovascular risk factors and bone mineral density in post menopausal women undergoing coronary angiography. Int J Cardiol 2008, 131:66–69.

    Article  PubMed  Google Scholar 

  13. Farhat GN, Cauley JA, Matthews KA, et al.: Volumetric BMD and vascular calcification in middle-aged women: the Study of Women’s Health Across the Nation. J Bone Miner Res 2006, 21:1839–1846.

    Article  PubMed  Google Scholar 

  14. Shen H, Bielak LF, Streeten EA, et al.: Relationship between vascular calcification and bone mineral density in the Old-order Amish. Calcif Tissue Int 2007, 80:244–250.

    Article  PubMed  CAS  Google Scholar 

  15. Sinnott B, Syed I, Sevrukov A, Barengolts E: Coronary calcification and osteoporosis in men and postmenopausal women are independent processes associated with aging. Calcif Tissue Int 2006, 78:195–202.

    Article  PubMed  CAS  Google Scholar 

  16. Adragao T, Branco P, Birne R, et al.: Bone mineral density, vascular calcifications, and arterial stiffness in peritoneal dialysis patients. Perit Dial Int 2008, 28:668–672.

    PubMed  Google Scholar 

  17. Al-Aly Z, Shao JS, Lai CF, et al.: Aortic Msx2-Wnt calcification cascade is regulated by TNF-alpha-dependent signals in diabetic Ldlr-/- mice. Arterioscler Thromb Vasc Biol 2007, 27:2589–2596.

    Article  PubMed  CAS  Google Scholar 

  18. Cheng SL, Shao JS, Cai J, et al.: Msx2 exerts bone anabolism via canonical Wnt signaling. J Biol Chem 2008, 283:20505–20522.

    Article  PubMed  CAS  Google Scholar 

  19. Lai CF, Seshadri V, Huang K, et al.: An osteopontin-NADPH oxidase signaling cascade promotes pro-matrix metalloproteinase 9 activation in aortic mesenchymal cells. Circ Res 2006, 98:1479–1489.

    Article  PubMed  CAS  Google Scholar 

  20. Aikawa E, Nahrendorf M, Figueiredo JL, et al.: Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation 2007, 116:2841–2850.

    Article  PubMed  CAS  Google Scholar 

  21. Tintut Y, Morony S, Demer LL: Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo. Arterioscler Thromb Vasc Biol 2004, 24:e6–e10.

    Article  PubMed  CAS  Google Scholar 

  22. Brodeur MR, Brissette L, Falstrault L, et al.: Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells. Free Radic Biol Med 2008, 44:506–517.

    Article  PubMed  CAS  Google Scholar 

  23. Hirasawa H, Tanaka S, Sakai A, et al.: ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells. J Bone Miner Res 2007, 22:1020–1030.

    Article  PubMed  CAS  Google Scholar 

  24. Huang MS, Morony S, Lu J, et al.: Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts. J Biol Chem 2007, 282:21237–21243.

    Article  PubMed  CAS  Google Scholar 

  25. Huang MS, Lu J, Ivanov Y, et al.: Hyperlipidemia impairs osteoanabolic effects of PTH. J Bone Miner Res 2008, 23:1672–1679.

    Article  PubMed  CAS  Google Scholar 

  26. Sebastian EM, Suva LJ, Friedman PA: Differential effects of intermittent PTH(1-34) and PTH(7-34) on bone microarchitecture and aortic calcification in experimental renal failure. Bone 2008, 43:1022–1030.

    Article  PubMed  CAS  Google Scholar 

  27. Shao JS, Cheng SL, Charlton-Kachigian N, et al.: Teriparatide (human parathyroid hormone (1-34)) inhibits osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice. J Biol Chem 2003, 278:50195–50202.

    Article  PubMed  CAS  Google Scholar 

  28. Bagger YZ, Rasmussen HB, Alexandersen P, et al.: Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se? Osteoporos Int 2007, 18:505–512.

    Article  PubMed  CAS  Google Scholar 

  29. Al-Jallad HF, Nakano Y, Chen JL, et al.: Transglutaminase activity regulates osteoblast differentiation and matrix mineralization in MC3T3-E1 osteoblast cultures. Matrix Biol 2006, 25:135–148.

    Article  PubMed  CAS  Google Scholar 

  30. Johnson KA, Polewski M, Terkeltaub RA: Transglutaminase 2 is central to induction of the arterial calcification program by smooth muscle cells. Circ Res 2008, 102:529–537.

    Article  PubMed  CAS  Google Scholar 

  31. Mikami S, Hamano T, Fujii N, et al.: Serum osteoprotegerin as a screening tool for coronary artery calcification score in diabetic pre-dialysis patients. Hypertens Res 2008, 31:1163–1170.

    Article  PubMed  CAS  Google Scholar 

  32. Frost ML, Grella R, Millasseau SC, 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 2008, 83:112–120.

    Article  PubMed  CAS  Google Scholar 

  33. Bucay N, Sarosi I, Dunstan CR, et al.: Osteoprotegerindeficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998, 12:1260–1268.

    Article  PubMed  CAS  Google Scholar 

  34. Bennett BJ, Scatena M, Kirk EA, et al.: Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice. Arterioscler Thromb Vasc Biol 2006, 26:2117–2124.

    Article  PubMed  CAS  Google Scholar 

  35. Morony S, Tintut Y, Zhang Z, et al.: Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr(-/-) mice. Circulation 2008, 117:411–420.

    Article  PubMed  CAS  Google Scholar 

  36. Orita Y, Yamamoto H, Kohno N, et al.: Role of osteoprotegerin in arterial calcification: development of new animal model. Arterioscler Thromb Vasc Biol 2007, 27:2058–2064.

    Article  PubMed  CAS  Google Scholar 

  37. Hofbauer LC, Schrader J, Niebergall U, et al.: Interleukin-4 differentially regulates osteoprotegerin expression and induces calcification in vascular smooth muscle cells. Thromb Haemost 2006, 95:708–714.

    PubMed  CAS  Google Scholar 

  38. Bakhireva LN, Laughlin GA, Bettencourt R, Barrett-Connor E: Does osteoprotegerin or receptor activator of nuclear factor-kappaB ligand mediate the association between bone and coronary artery calcification? J Clin Endocrinol Metab 2008, 93:2009–2012.

    Article  PubMed  CAS  Google Scholar 

  39. Fiore CE, Celotta G, Politi GG, et al.: Association of high alpha2-Heremans-Schmid glycoprotein/fetuin concentration in serum and intima-media thickness in patients with atherosclerotic vascular disease and low bone mass. Atherosclerosis 2007, 195:110–115.

    Article  PubMed  CAS  Google Scholar 

  40. Karasik D, Kiel DP, Kiely DK, et al.: Abdominal aortic calcification and exostoses at the hand and lumbar spine: the Framingham Study. Calcif Tissue Int 2006, 78:1–8.

    Article  PubMed  CAS  Google Scholar 

  41. Price PA, Chan WS, Jolson DM, Williamson MK: The elastic lamellae of devitalized arteries calcify when incubated in serum: evidence for a serum calcification factor. Arterioscler Thromb Vasc Biol 2006, 26:1079–1085.

    Article  PubMed  CAS  Google Scholar 

  42. Price PA, Roublick AM, Williamson MK: Artery calcification in uremic rats is increased by a low protein diet and prevented by treatment with ibandronate. Kidney Int 2006, 70:1577–1583.

    Article  PubMed  CAS  Google Scholar 

  43. Tamagaki K, Yuan Q, Ohkawa H, et al.: Severe hyperparathyroidism with bone abnormalities and metastatic calcification in rats with adenine-induced uraemia. Nephrol Dial Transplant 2006, 21:651–659.

    Article  PubMed  Google Scholar 

  44. Wilund KR, Tomayko EJ, Evans EM, et al.: Physical activity, coronary artery calcium, and bone mineral density in elderly men and women: a preliminary investigation. Metabolism 2008, 57:584–591.

    Article  PubMed  CAS  Google Scholar 

  45. Lee CD, Jacobs DR Jr, Hankinson A, et al.: Cardiorespiratory fitness and coronary artery calcification in young adults: the CARDIA Study. Atherosclerosis 2009, 203:263–268.

    Article  PubMed  CAS  Google Scholar 

  46. Adami S, Gatti D, Viapiana O, et al.: Physical activity and bone turnover markers: a cross-sectional and a longitudinal study. Calcif Tissue Int 2008, 83:388–392.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, BH-307 Center for Health Sciences, 10833, LeConte Avenue, Los Angeles, CA, 90095-1679, USA

    Linda L. Demer

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  1. Linda L. Demer
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  2. Yin Tintut
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Correspondence to Linda L. Demer.

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Demer, L.L., Tintut, Y. Mechanisms linking osteoporosis with cardiovascular calcification. Curr Osteoporos Rep 7, 42–46 (2009). https://doi.org/10.1007/s11914-009-0008-1

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  • DOI: https://doi.org/10.1007/s11914-009-0008-1

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