Exploring the Links Between Common Diseases of Ageing—Osteoporosis, Sarcopenia and Vascular Calcification

  • Alexander J. RodriguezEmail author
  • David Scott
  • Peter R. Ebeling
Review Paper


Vascular diseases account for a significant proportion of preventable deaths, particularly in developed countries. Our understanding of diseases that alter the structure and function of blood vessels such as vascular calcification and vascular stiffness has grown enormously such that we now appreciate them to be active processes that can be modified. Interest has also grown in examining the links between other diseases of ageing such as the loss of bone (osteoporosis) and muscle (sarcopenia) with the development and progression of vascular disease as these three disease states commonly co-occur in older age. Cardiovascular disease (including calcification and arterial stiffness) is highly prevalent in older populations and it appears that its progression is accelerated in patients with osteoporosis, fracture, sarcopenia and in those who are functionally impaired. Biological and clinical evidence supports a view that vascular disease (calcification/stiffness) may be both a cause and consequence of diseases of ageing including musculoskeletal decline. This review provides an overview of the development of vascular calcification and stiffness and explores the molecular and physiological mechanisms linking osteoporosis and sarcopenia to vascular disease development. This review also examines clinical evidence supporting the association of muscle and bone loss with vascular disease and concludes by reviewing the interventional and therapeutic potential of bone-active minerals and hormones (calcium and vitamin D) on cardiovascular disease biology, given that these represent potential interventions to target multiple body systems. Overall, this review will aim to highlight the underappreciated burden of cardiovascular disease in individuals in the context of musculoskeletal diseases.


Osteoporosis Sarcopenia Vascular calcification Cardiovascular disease Calcium Vitamin D 



No funding was required in undertaking this work.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval

No ethics committee approval was required in undertaking this work.

Informed Consent

No informed consent was required in undertaking this work as work did not involve any human participants or animals.


  1. 1.
    Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002;359:1929–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999;353:878–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Seeman E. Invited review: pathogenesis of osteoporosis. J Appl Physiol. 2003;95(5):2142–51.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Wade SW, Strader C, Fitzpatrick LA, Anthony MS, O’Malley CD. Estimating prevalence of osteoporosis: examples from industrialized countries. Arch Osteoporos. 2014;9(1):182.PubMedCrossRefGoogle Scholar
  5. 5.
    Sanders KM, Seeman E, Ugoni AM, et al. Age-and Gender-Specific Rate of Fractures in Australia: A Population-Based Study Accessed 20 Aug 2018.
  6. 6.
    Mithal A, Bansal B, Kyer C, Ebeling P. The Asia-Pacific Regional Audit-Epidemiology, Costs, and Burden of Osteoporosis in India 2013: A Report of International Osteoporosis Foundation. Indian J Endocrinol Metab. 2014;18:449.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465–75.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337:670–6.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336:262–6.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010;341:c3691.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Licata AA. Discovery, clinical development, and therapeutic uses of bisphosphonates. Ann Pharmacother. 2005;39(4):668–77.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest. 1996;97:2692–6.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, et al. Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab. Nat Rev Drug Discov. 2012;11(5):401–19.CrossRefGoogle Scholar
  15. 15.
    Satterwhite J, Heathman M, Miller PD, Marín F, Glass EV, Dobnig H. Pharmacokinetics of teriparatide (rhPTH[1-34]) and calcium pharmacodynamics in postmenopausal women with osteoporosis. Calcif Tissue Int. 2010;87:485–92.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Brixen KT, Christensen B, Ejersted C, Langdahl BL. Teriparatide (biosynthetic human parathyroid hormone 1-34): a new paradigm in the treatment of osteoporosis. Pharmacol Toxicol. 2004;94(6):260–70.CrossRefGoogle Scholar
  17. 17.
    Brennan T, Rybchyn M, Green W, Atwa S, Conigrave A, Mason R. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol. 2009;157:1291–300.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Kanis JA, McCloskey EV. Risk factors in osteoporosis. Maturitas. 1998;30(3):229–33.PubMedCrossRefGoogle Scholar
  19. 19.
    Kanis JA, Harvey NC, Johansson H, Odén A, McCloskey EV, Leslie WD. Overview of fracture prediction tools. J Clin Densitom. 2017;20:444–50.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Nguyen TV, Eisman JA. Fracture risk assessment: from population to individual. J Clin Densitom. 2017;20:368–78.PubMedCrossRefGoogle Scholar
  21. 21.
    Iwaniec UT, Turner RT. Influence of body weight on bone mass, architecture and turnover. J Endocrinol. 2016;230:R115–30.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Kerckhofs G, Durand M, Vangoitsenhoven R, Marin C, van der Schueren B, Carmeliet G, et al. Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography. Sci Rep. 2016;6(1):35517.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Liu C-T, Broe KE, Zhou Y, Boyd SK, Cupples LA, Hannan MT, et al. Visceral adipose tissue is associated with bone microarchitecture in the Framingham osteoporosis study. J Bone Miner Res. 2017;32(1):143–50.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Nielson CM, Srikanth P, Orwoll ES. Obesity and fracture in men and women: an epidemiologic perspective. J Bone Miner Res. 2012;27:1–10.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Marcus RL, Addison O, Kidde JP, Dibble LE, Lastayo PC. Skeletal muscle fat infiltration: impact of age, inactivity, and exercise. J Nutr Health Aging. 2010;14:362–6.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Scott D, Shore-Lorenti C, McMillan LB, et al. Calf muscle density is independently associated with physical function in overweight and obese older adults. J Musculoskelet Neuronal Interact. 2018;18:9–17.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Scott D, Shore-Lorenti C, McMillan L, et al. Associations of components of sarcopenic obesity with bone health and balance in older adults. Arch Gerontol Geriatr. 2018;75:125–31.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Szulc P, Samelson EJ, Kiel DP, Delmas PD. Increased bone resorption is associated with increased risk of cardiovascular events in men: the MINOS study. J Bone Miner Res. 2009;24:2023–31.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Yang S, Chen A, Wu T. Association of history of fracture with prehypertension and hypertension: a retrospective case-control study. BMC Musculoskelet Disord. 2015;16:86.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Sennerby U, Melhus H, Gedeborg R, et al. Cardiovascular diseases and risk of hip fracture. JAMA. 2009;302:1666.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Fricke O, Beccard R, Semler O, Schoenau E. Analyses of muscular mass and function: the impact on bone mineral density and peak muscle mass. Pediatr Nephrol. 2010;25:2393–400.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Tsuda K, Nishio I, Masuyama Y. Bone mineral density in women with essential hypertension. Am J Hypertens. 2001;14:704–7.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Jorgensen L, Joakimsen O, Rosvold Berntsen GK, Heuch I, Jacobsen BK. Low bone mineral density is related to echogenic carotid artery plaques: a population-based study. Am J Epidemiol. 2004;160:549–56.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Tanko LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA, Cummings SR. Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Miner Res. 2005;20(11):1912–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Wong CX, Gan SW, Lee SW, et al. Atrial fibrillation and risk of hip fracture: a population-based analysis of 113,600 individuals. Int J Cardiol. 2017;243:229–32.PubMedCrossRefGoogle Scholar
  36. 36.
    Cappuccio FP, Meilahn E, Zmuda JM, Cauley JA. High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group. Lancet. 1999;354:971–5.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Sennerby U, Farahmand B, Ahlbom A, Ljunghall S, Michaelsson K. Cardiovascular diseases and future risk of hip fracture in women. Osteoporos Int. 2007;18:1355–62.PubMedCrossRefGoogle Scholar
  38. 38.
    Bagger YZ, Tanko LB, Alexandersen P, Qin G, Christiansen C. 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.PubMedCrossRefGoogle Scholar
  39. 39.
    Jorgensen L, Joakimsen O, Mathiesen EB, et al. Carotid plaque echogenicity and risk of nonvertebral fractures in women: a longitudinal population-based study. Calcif Tissue Int. 2006;79:207–13.PubMedCrossRefGoogle Scholar
  40. 40.
    Scott D, Blizzard L, Fell J, Jones G. The epidemiology of sarcopenia in community living older adults: what role does lifestyle play? J Cachexia Sarcopenia Muscle. 2011;2(3):125–34.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Bischoff-Ferrari HA, Orav JE, Kanis JA, et al. Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporos Int. 2015;26:2793–802.PubMedCrossRefGoogle Scholar
  42. 42.
    Patel HP, Syddall HE, Jameson K, Robinson S, Denison H, Roberts HC, et al. Prevalence of sarcopenia in community-dwelling older people in the UK using the European working group on sarcopenia in older people (EWGSOP) definition: findings from the Hertfordshire cohort study (HCS). Age Ageing. 2013;42(3):378–84.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Yamada M, Nishiguchi S, Fukutani N, et al. Prevalence of sarcopenia in community-dwelling Japanese older adults. J Am Med Dir Assoc. 2013;14:911–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Waters DL, Baumgartner RN, Garry PJ. Sarcopenia: current perspectives. J Nutr Health Aging. 2000;4:133–9.PubMedGoogle Scholar
  45. 45.
    Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90(6):1579–85.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Miljkovic I, Kuipers AL, Cauley JA, et al. Greater skeletal muscle fat infiltration is associated with higher all-cause and cardiovascular mortality in older men. J Gerontol A Biol Sci Med Sci. 2015;70:1133–40.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Scott D, Trbojevic T, Skinner E, Clark RA, Levinger P, Haines TP, et al. Associations of calf inter- and intra-muscular adipose tissue with cardiometabolic health and physical function in community-dwelling older adults. J Musculoskelet Neuronal Interact. 2015;15(4):350–7.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Rosique-Esteban N, Babio N, Díaz-López A, et al. Leisure-time physical activity at moderate and high intensity is associated with parameters of body composition, muscle strength and sarcopenia in aged adults with obesity and metabolic syndrome from the PREDIMED-Plus study. Clin Nutr. 2018; published online June 6.
  49. 49.
    Kim J, Lee Y, Kye S, Chung Y-S, Kim K-M. Association between healthy diet and exercise and greater muscle mass in older adults. J Am Geriatr Soc. 2015;63:886–92.PubMedCrossRefGoogle Scholar
  50. 50.
    Reid KF, Martin KI, Doros G, et al. Comparative effects of light or heavy resistance power training for improving lower extremity power and physical performance in mobility-limited older adults. J Gerontol A Biol Sci Med Sci. 2015;70:374–80.PubMedCrossRefGoogle Scholar
  51. 51.
    PETERSON MD, SEN A, GORDON PM. Influence of resistance exercise on lean body mass in aging adults. Med Sci Sport Exerc. 2011;43:249–58.CrossRefGoogle Scholar
  52. 52.
    Campbell WW, Trappe TA, Wolfe RR, Evans WJ. The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. J Gerontol A Biol Sci Med Sci. 2001;56:M373–80.PubMedCrossRefGoogle Scholar
  53. 53.
    Morris MS, Jacques PF. Total protein, animal protein and physical activity in relation to muscle mass in middle-aged and older Americans. Br J Nutr. 2013;109:1294–303.PubMedCrossRefGoogle Scholar
  54. 54.
    Granic A, Mendonça N, Sayer AA, et al. Low protein intake, muscle strength and physical performance in the very old: The Newcastle 85+ Study. Clin Nutr. 2017; published online Nov 16. Scholar
  55. 55.
    Gonzalez-Freire M, de Cabo R, Studenski SA, Ferrucci L. The neuromuscular junction: aging at the crossroad between nerves and muscle. Front Aging Neurosci. 2014;6:208.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JAE, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev. 2012;33(3):456–92.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Scott D, Blizzard L, Fell J, Giles G, Jones G. Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: the Tasmanian older adult cohort study. J Am Geriatr Soc. 2010;58:2129–34.PubMedCrossRefGoogle Scholar
  58. 58.
    Rousseau A-F, Foidart-Desalle M, Ledoux D, Remy C, Croisier JL, Damas P, et al. Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: a one-year pilot randomized controlled trial in adults with severe burns. Burns. 2015;41(2):317–25.PubMedCrossRefGoogle Scholar
  59. 59.
    van Dronkelaar C, van Velzen A, Abdelrazek M, van der Steen A, Weijs PJM, Tieland M. Minerals and Sarcopenia; The Role of Calcium, Iron, Magnesium, Phosphorus, Potassium, Selenium, Sodium, and Zinc on Muscle Mass, Muscle Strength, and Physical Performance in Older Adults: A Systematic Review. J Am Med Dir Assoc. 2018;19:6–11.e3.PubMedCrossRefGoogle Scholar
  60. 60.
    Bo Y, Liu C, Ji Z, et al. A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: A double-blind randomized controlled trial. Clin Nutr. 2018; published online Jan 9.
  61. 61.
    Bauer JM, Verlaan S, Bautmans I, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015;16:740–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Beaudart C, Dawson A, Shaw SC, et al. Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review. Osteoporos Int. 2017;28:1817–33.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Antoniak AE, Greig CA. The effect of combined resistance exercise training and vitamin D 3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis. BMJ Open. 2017;7:e014619.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Trajanoska K, Schoufour JD, Darweesh SK, et al. Sarcopenia and its clinical correlates in the general population: the Rotterdam study. J Bone Miner Res. 2018;33:1209–18.PubMedCrossRefGoogle Scholar
  65. 65.
    Atkins JL, Whincup PH, Morris RW, Lennon LT, Papacosta O, Wannamethee SG. Sarcopenic obesity and risk of cardiovascular disease and mortality: a population-based cohort study of older men. J Am Geriatr Soc. 2014;62:253–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Chuang S-Y, Chang H-Y, Lee M-S, Chia-Yu Chen R, Pan W-H. Skeletal muscle mass and risk of death in an elderly population. Nutr Metab Cardiovasc Dis. 2014;24:784–91.PubMedCrossRefGoogle Scholar
  67. 67.
    Cardiovascular disease: Australian facts 2011. Canberra, 2011. Accessed 9 Jan 2018.
  68. 68.
    Australian Institute of Health and Welfare. Cardiovascular Disease in Australia 2018. 2018. Accessed 7 Jul 2018.
  69. 69.
    Tsamis A, Krawiec JT, Vorp DA. Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review. J R Soc Interface. 2013;10:20121004.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Speer MY, Yang H-Y, Brabb T, et al. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res. 2009;104:733–41.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Zhu D, Mackenzie NCW, Millán JL, Farquharson C, MacRae VE. The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One. 2011;6:e19595.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Pugliese G, Iacobini C, Fantauzzi CB, Menini S. The dark and bright side of atherosclerotic calcification. Atherosclerosis. 2015;238. Scholar
  73. 73.
    Wolinsky H, Glagov S. A lamellar unit of aortic medial structure and function in mammals. Am Hear Assoc Accessed 26 Mar 2018.
  74. 74.
    Ooshima A, Fuller GC, Cardinale GJ, Spector S, Udenfriend S. Increased collagen synthesis in blood vessels of hypertensive rats and its reversal by antihypertensive agents. Proc Natl Acad Sci U S A. 1974;71:3019–23.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Shang X, Scott D, Hodge A, et al. Adiposity assessed by anthropometric measures has a similar or greater predictive ability than dual-energy X-ray absorptiometry measures for abdominal aortic calcification in community-dwelling older adults. Int J Card Imaging. 2016;32:1451–60.CrossRefGoogle Scholar
  76. 76.
    Norman PE, Jamrozik K, Lawrence-Brown MM, et al. Population based randomised controlled trial on impact of screening on mortality from abdominal aortic aneurysm. BMJ. 2004;329:1259.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Murphy WA, Zur ND, Gostner P, Knapp R, Recheis W, Seidler H. The Iceman: Discovery and Imaging. Radiology. 2003;226:614–29.PubMedCrossRefGoogle Scholar
  78. 78.
    Virchow R. Cellular pathology. As based upon physiological and pathological histology. Lecture XVI--atheromatous affection of arteries. 1858. Nutr Rev. 1989;47:23–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Lehto S, Niskanen L, Suhonen M, Rönnemaa T, Laakso M. Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996;16:978–83.PubMedCrossRefGoogle Scholar
  80. 80.
    Lewis JR, Schousboe JT, Lim WH, Wong G, Zhu K, Lim EM, et al. Abdominal aortic calcification identified on lateral spine images from bone densitometers are a marker of generalized atherosclerosis in elderly women. Arterioscler Thromb Vasc Biol. 2016;36(1):166–73.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Lewis J, Schousboe J, Lim W, et al. Abdominal aortic calcification identified on images from bone densitometers and long-term cardiovascular outcomes in elderly women. J Bone Miner Res Conf. 2016;31.
  82. 82.
    Ishii T, Asuwa N. Collagen and elastin degradation by matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in aortic dissection. Hum Pathol. 2000;31:640–6.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Rattazzi M, Rosenfeld ME. The multifaceted role of macrophages in cardiovascular calcification. Atherosclerosis. 2018; published online Feb 1. Scholar
  84. 84.
    Loree HM, Tobias BJ, Gibson LJ, Kamm RD, Small DM, Lee RT. Mechanical properties of model atherosclerotic lesion lipid pools. Arterioscler Thromb. 1994;14:230–4.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Cho I-J, Chang H-J, Park H-B, et al. Aortic calcification is associated with arterial stiffening, left ventricular hypertrophy, and diastolic dysfunction in elderly male patients with hypertension. J Hypertens. 2015;33:1633–41.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Wagenseil JE, Mecham RP. Elastin in large artery stiffness and hypertension. J Cardiovasc Transl Res. 2012;5:264–73.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Guo J, Fujiyoshi A, Willcox B, et al. Increased Aortic Calcification Is Associated With Arterial Stiffness Progression in Multiethnic Middle-Aged Men. Hypertension. 2017;69:102–8.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Chien S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol. 2007;292:H1209–24.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Yang JW, Cho KI, Kim JH, et al. Wall shear stress in hypertensive patients is associated with carotid vascular deformation assessed by speckle tracking strain imaging. Clin Hypertens. 2014;20:10.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Nicoll R, Henein M. Arterial calcification: a new perspective? Int J Cardiol. 2017;228:11–22.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Schousboe JT, Taylor BC, Kiel DP, Ensrud KE, Wilson KE, McCloskey EV. 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(3):409–16.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW. New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis. 1997;132:245–50.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Laurent S, Boutouyrie P, Asmar R, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236–41.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Hametner B, Wassertheurer S, Kropf J, Mayer C, Eber B, Weber T. Oscillometric estimation of aortic pulse wave velocity. Blood Press Monit. 2013;18:173–6.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Lewis JR, Schousboe JT, Lim WH, et al. J Bone Miner Res. 2018; published online Feb 14. Scholar
  97. 97.
    Witteman JM, Kok F, Van Saase JCM, Valkenburg H. Aortic calcification as a predictor of cardiovascular mortality. Lancet. 1986;328:1120–2.CrossRefGoogle Scholar
  98. 98.
    Nielsen ML, Pareek M, Gerke O, et al. Uncontrolled hypertension is associated with coronary artery calcification and electrocardiographic left ventricular hypertrophy: a case-control study. J Hum Hypertens. 2015;29:303–8.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Issever AS, Kentenich M, Kohlitz T, Diederichs G, Zimmermann E. Osteoporosis and atherosclerosis: a post-mortem MDCT study of an elderly cohort. Eur Radiol. 2013;23(10):2823–9.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW. Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham heart study. [erratum appears in Calcif tissue Int. 2004 Feb;74(2):208]. Calcif Tissue Int. 2001;68:271–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Cai T, Sun D, Duan Y, Wen P, Dai C, Yang J, et al. WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression. Exp Cell Res. 2016;345(2):206–17.PubMedCrossRefGoogle Scholar
  102. 102.
    Vega OA, Lucero CMJ, Araya HF, et al. Wnt/β-catenin signaling activates expression of the bone-related transcription factor RUNX2 in select human osteosarcoma cell types. J Cell Biochem. 2017;118:3662–74.PubMedCrossRefGoogle Scholar
  103. 103.
    Shi L, Cai G, Shi J, et al. Ossification of the posterior ligament is mediated by osterix via inhibition of the β-catenin signaling pathway. Exp Cell Res. 2016;349:53–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Moon YJ, Yun C-Y, Lee J-C, Kim JR, Park B-H, Cho E-S. Maturation of cortical bone suppresses periosteal osteoprogenitor proliferation in a paracrine manner. J Mol Histol. 2016;47:445–53.PubMedCrossRefGoogle Scholar
  105. 105.
    Kook S-H, Heo JS, Lee J-C. Crucial roles of canonical Runx2-dependent pathway on Wnt1-induced osteoblastic differentiation of human periodontal ligament fibroblasts. Mol Cell Biochem. 2015;402:213–23.PubMedCrossRefGoogle Scholar
  106. 106.
    Yu S, Yerges-Armstrong LM, Chu Y, Zmuda JM, Zhang Y. AP2 suppresses osteoblast differentiation and mineralization through down-regulation of Frizzled-1. Biochem J. 2015;465:395–404.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Yuan L-Q, Zhu J-H, Wang H-W, et al. RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells. PLoS One. 2011;6:e29037.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Malyankar UM, Scatena M, Suchland KL, Yun TJ, Clark EA, Giachelli CM. Osteoprotegerin is an α v β 3 -induced, NF-κB-dependent survival factor for endothelial cells. J Biol Chem. 2000;275:20959–62.PubMedCrossRefGoogle Scholar
  109. 109.
    Sun Y, Byon CH, Yuan K, et al. Smooth muscle cell-specific Runx2 deficiency inhibits vascular calcification. Circ Res. 2012;111:543–52.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Zhang K, Zhang Y, Feng W, et al. Interleukin-18 Enhances Vascular Calcification and Osteogenic Differentiation of Vascular Smooth Muscle Cells Through TRPM7 Activation. Arterioscler Thromb Vasc Biol. 2017;37(10):1933–43.PubMedCrossRefGoogle Scholar
  111. 111.
    Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–43.CrossRefGoogle Scholar
  112. 112.
    Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of Romosozumab in men with osteoporosis. J Clin Endocrinol Metab. 2018;103(9):3183–93.PubMedCrossRefGoogle Scholar
  113. 113.
    Touw WA, Ueland T, Bollerslev J, Schousboe JT, Lim WH, Wong G, et al. Association of Circulating Wnt Antagonists with Severe Abdominal Aortic Calcification in elderly women. J Endocr Soc. 2017;1(1):26–38.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML. The relationship between inhibitors of the Wnt signalling pathway (Dickkopf-1(DKK1) and sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone. 2013;56:42–7.PubMedCrossRefGoogle Scholar
  115. 115.
    Krishna SM, Seto S-W, Jose RJ, et al. Wnt signaling pathway inhibitor Sclerostin inhibits angiotensin II–induced aortic aneurysm and AtherosclerosisHighlights. Arterioscler Thromb Vasc Biol. 2017;37:553–66.PubMedCrossRefGoogle Scholar
  116. 116.
    Acıbucu F, Dokmetas H, Acıbucu D, Kılıclı F, Aydemir M, Cakmak E. Effect of vitamin D treatment on serum Sclerostin level. Exp Clin Endocrinol Diabetes. 2017;125:634–7.PubMedCrossRefGoogle Scholar
  117. 117.
    Sankaralingam A, Roplekar R, Turner C, Dalton RN, Hampson G. Changes in Dickkopf-1 (DKK1) and Sclerostin following a loading dose of vitamin D 2 (300,000 IU). J Osteoporos. 2014;2014:682763.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr. 2013;32:970–5.PubMedCrossRefGoogle Scholar
  119. 119.
    Larsen T, Mose FH, Bech JN, Hansen AB, Pedersen EB. Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. Am J Hypertens. 2012;25:1215–22.PubMedCrossRefGoogle Scholar
  120. 120.
    Dreyer G, Tucker AT, Harwood SM, Pearse RM, Raftery MJ, Yaqoob MM. Ergocalciferol and microcirculatory function in chronic kidney disease and concomitant vitamin D deficiency: an exploratory, double blind, Randomised Controlled Trial. PLoS One. 2014;9:e99461.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Rejnmark L, Bislev LS, Cashman KD, et al. Non-skeletal health effects of vitamin D supplementation: a systematic review on findings from meta-analyses summarizing trial data. PLoS One. 2017;12:e0180512.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Sambrook PN, Chen JS, Simpson JM, March LM. Impact of adverse news media on prescriptions for osteoporosis: effect on fractures and mortality. Med J Aust. 2010;193(3):154–6.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Kranenburg G, Bartstra JW, Weijmans M, et al. Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis. 2016;252:106–15.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Kawahara T, Nishikawa M, Kawahara C, Inazu T, Sakai K, Suzuki G. Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial. Circulation. 2013;127:2327–35.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Effect of alendronate on vascular calcification in CKD stages 3 and 4: a pilot randomized controlled trial. Am J Kidney Dis. 2010;56:57–68.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Cummings SR, Martin JS, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.CrossRefGoogle Scholar
  127. 127.
    Samelson EJ, Miller PD, Christiansen C, et al. RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk. J Bone Miner Res. 2014;29:450–7.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Ueki K, Yamada S, Tsuchimoto A, et al. Rapid progression of vascular and soft tissue calcification while being managed for severe and persistent hypocalcemia induced by Denosumab treatment in a patient with multiple myeloma and chronic kidney disease. Intern Med. 2015;54:2637–42.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Scott D, Blizzard L, Fell J, Jones G. Prospective associations between ambulatory activity, body composition and muscle function in older adults. Scand J Med Sci Sports. 2011;21:e168–75.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Tarantino G, Costantini S, Finelli C, et al. Is serum Interleukin-17 associated with early atherosclerosis in obese patients? J Transl Med. 2014;12:214.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Alexandersen P, Tankó LB, Bagger YZ, Jespersen J, Skouby SO, Christiansen C. Associations between aortic calcification and components of body composition in elderly men*. Obesity. 2006;14:1571–8.PubMedCrossRefGoogle Scholar
  132. 132.
    Szulc P, Hofbauer LC, Rauner M, Goettsch C, Chapurlat R, Schoppet M. Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study. Eur J Endocrinol. 2012;167:873–80.PubMedCrossRefGoogle Scholar
  133. 133.
    Jensky NE, Allison MA, Loomba R, et al. Null association between abdominal muscle and calcified atherosclerosis in community-living persons without clinical cardiovascular disease: the multi-ethnic study of atherosclerosis. Metabolism. 2013;62:1562–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Idoate F, Cadore EL, Casas-Herrero A, et al. Adipose tissue compartments, muscle mass, muscle fat infiltration, and coronary calcium in institutionalized frail nonagenarians. Eur Radiol. 2015;25:2163–75.PubMedCrossRefGoogle Scholar
  135. 135.
    Wassel CL, Laughlin GA, Saad SD, Araneta MRG, Wooten W, Barrett-Connor E, et al. Associations of abdominal muscle area with 4-year change in coronary artery calcium differ by ethnicity among post-menopausal women. Ethn Dis. 2015;25(4):435–42.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Ko B-J, Chang Y, Jung H-S, et al. Relationship between low relative muscle mass and coronary artery calcification in healthy AdultsSignificance. Arterioscler Thromb Vasc Biol. 2016;36:1016–21.PubMedCrossRefGoogle Scholar
  137. 137.
    Idoate F, Cadore EL, Casas-Herrero A, et al. Noncoronary vascular calcification, bone mineral density, and muscle mass in institutionalized frail nonagenarians. Rejuvenation Res. 2017;20:298–308.PubMedCrossRefGoogle Scholar
  138. 138.
    Spahillari A, Mukamal KJ, DeFilippi C, et al. The association of lean and fat mass with all-cause mortality in older adults: the cardiovascular health study. Nutr Metab Cardiovasc Dis. 2016;26:1039–47.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Chuang S-Y, Hsu Y-Y, Chen RC-Y, Liu W-L, Pan W-H. Abdominal obesity and low skeletal muscle mass jointly predict Total mortality and cardiovascular mortality in an elderly Asian population. J Gerontol A Biol Sci Med Sci. 2016;71(8):1049–55.PubMedCrossRefGoogle Scholar
  140. 140.
    Elliott B, Renshaw D, Getting S, Mackenzie R. The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiol. 2012;205:324–40.CrossRefGoogle Scholar
  141. 141.
    Hamrick MW, Shi X, Zhang W, Pennington C, Thakore H, Haque M, et al. Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading. Bone. 2007;40(6):1544–53.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Artaza JN, Singh R, Ferrini MG, Braga M, Tsao J, Gonzalez-Cadavid NF. Myostatin promotes a fibrotic phenotypic switch in multipotent C3H 10T1/2 cells without affecting their differentiation into myofibroblasts. J Endocrinol. 2008;196:235–49.PubMedCrossRefGoogle Scholar
  143. 143.
    Saely CH, Dyballa T, Vonbank A, et al. Type 2 diabetes but not coronary atherosclerosis is an independent determinant of impaired mobility in angiographied coronary patients. Diabetes Res Clin Pract. 2008;82:185–9.PubMedCrossRefGoogle Scholar
  144. 144.
    Abizanda Soler P, Paterna Mellinas G, Martín Sebastiá E, Casado Moragón L, López Jiménez E, Martínez SE. Aterosclerosis subclínica, un predictor de limitación funcional al año en ancianos con alto nivel funcional: estudio Albacete. Rev Esp Geriatr Gerontol. 2010;45:125–30.PubMedCrossRefGoogle Scholar
  145. 145.
    Den Ouden MEM, Schuurmans MJ, Arts EMA, et al. Atherosclerosis and physical functioning in older men, a longitudinal study. J Nutr Health Aging. 2013;17:97–104.CrossRefGoogle Scholar
  146. 146.
    Park J, Park H. Muscle strength and carotid artery flow velocity is associated with increased risk of atherosclerosis in adults. Cardiol J. 2017;24:385–92.PubMedCrossRefGoogle Scholar
  147. 147.
    Shimizu Y, Sato S, Koyamatsu J, et al. Handgrip strength and subclinical carotid atherosclerosis in relation to platelet levels among hypertensive elderly Japanese. Oncotarget. 2017;8:69362–9.PubMedPubMedCentralGoogle Scholar
  148. 148.
    Suwa M, Imoto T, Kida A, Yokochi T, Iwase M, Kozawa K. Association of body flexibility and carotid atherosclerosis in Japanese middle-aged men: a cross-sectional study. BMJ Open. 2018;8:e019370.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Everson-Rose SA, Mendes de Leon CF, Roetker NS, Lutsey PL, Alonso A. Subclinical cardiovascular disease and changes in self-reported mobility: multi-ethnic study of atherosclerosis. Journals Gerontol A Biol Sci Med Sci. 2018;73:218–24.CrossRefGoogle Scholar
  150. 150.
    Jadczak AD, Makwana N, Luscombe-Marsh N, Visvanathan R, Schultz TJ. Effectiveness of exercise interventions on physical function in community-dwelling frail older people. JBI Database System Rev Implement Rep. 2018;16:752–75.PubMedCrossRefGoogle Scholar
  151. 151.
    Lai C-C, Tu Y-K, Wang T-G, Huang Y-T, Chien K-L. Effects of resistance training, endurance training and whole-body vibration on lean body mass, muscle strength and physical performance in older people: a systematic review and network meta-analysis. Age Ageing. 2018;47(3):367–73.CrossRefGoogle Scholar
  152. 152.
    Rossow LM, Fahs CA, Thiebaud RS, et al. Arterial stiffness and blood flow adaptations following eight weeks of resistance exercise training in young and older women. Exp Gerontol. 2014;53:48–56.PubMedCrossRefGoogle Scholar
  153. 153.
    Shiotsu Y, Watanabe Y, Tujii S, Yanagita M. Effect of exercise order of combined aerobic and resistance training on arterial stiffness in older men. Exp Gerontol. 2018;111:27–34.PubMedCrossRefGoogle Scholar
  154. 154.
    Green D, Cheetham C, Mavaddat L, Watts K, Best M, Taylor R, et al. Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide. Am J Physiol Heart Circ Physiol. 2002;283(3):H899–907.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Endes S, Schaffner E, Caviezel S, et al. Long-term physical activity is associated with reduced arterial stiffness in older adults: longitudinal results of the SAPALDIA cohort study. Age Ageing. 2016;45:110–5.PubMedCrossRefGoogle Scholar
  156. 156.
    Wildman RP, Mackey RH, Bostom A, Thompson T, Sutton-Tyrrell K. Measures of obesity are associated with vascular stiffness in young and older adults. Hypertension. 2003;42:468–73.PubMedCrossRefGoogle Scholar
  157. 157.
    Jarrell JC, Morin J, Vasquez K, Cuneo GJ, Kossodo S, Peterson JD. Imaging of Cathepsin K activity in rodent models of bone turnover and soft tissue calcification. Mol Imaging Biol. 2012;1:S1741.Google Scholar
  158. 158.
    Shanbhogue VV, Støving RK, Frederiksen KH, Hanson S, Brixen K, Gram J, et al. Bone structural changes after gastric bypass surgery evaluated by HR-pQCT: a two-year longitudinal study. Eur J Endocrinol. 2017;176(6):685–93.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Szulc P, Schoppet M, Goettsch C, et al. Endocrine and clinical correlates of Myostatin serum concentration in men—the STRAMBO study. J Clin Endocrinol Metab. 2012;97:3700–8.PubMedCrossRefPubMedCentralGoogle Scholar
  160. 160.
    Aihara K, Azuma H, Akaike M, et al. Disruption of nuclear vitamin D receptor gene causes enhanced Thrombogenicity in mice. J Biol Chem. 2004;279:35798–802.PubMedCrossRefGoogle Scholar
  161. 161.
    Chen S, Law CS, Grigsby CL, et al. Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac HypertrophyClinical perspective. Circulation. 2011;124:1838–47.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014;114:379–93.PubMedCrossRefGoogle Scholar
  163. 163.
    Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol. 2003;41:105–12.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 164.
    Al Mheid I, Patel R, Murrow J, et al. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011;58:186–92.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Tomson J, Hin H, Emberson J, et al. Effects of vitamin D on blood pressure, arterial stiffness, and cardiac function in older people after 1 year: BEST-D (biochemical efficacy and safety trial of vitamin D). J Am Heart Assoc. 2017;6:e005707.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Sluyter JD, Camargo CA, Stewart AW, et al. Effect of monthly, high-dose, Long-Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy. J Am Heart Assoc. 2017;6:e006802.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Witte KK, Byrom R, Gierula J, et al. Effects of vitamin D on cardiac function in patients with chronic HF: the VINDICATE study. J Am Coll Cardiol. 2016;67:2593–603.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Chung M, Tang AM, Fu Z, Wang DD, Newberry SJ. Calcium intake and cardiovascular disease risk. Ann Intern Med. 2016;165:856.PubMedCrossRefGoogle Scholar
  169. 169.
    Reid IR, Gamble GD, Bolland MJ. Circulating calcium concentrations, vascular disease and mortality: a systematic review. J Intern Med. 2016;279(6):524–40.PubMedCrossRefGoogle Scholar
  170. 170.
    Harvey NC, Biver E, Kaufman J-M, Bauer J, Branco J, Brandi ML, et al. The role of calcium supplementation in healthy musculoskeletal ageing. Osteoporos Int. 2017;28(2):447–62.PubMedCrossRefGoogle Scholar
  171. 171.
    Michaelsson K, Melhus H, Warensjo Lemming E, Wolk A, Byberg L. Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ. 2013;346:f228.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Khan B, Nowson CA, Daly RM, et al. Higher dietary calcium intakes are associated with reduced risks of fractures, cardiovascular events, and mortality: a prospective cohort study of older men and women. J Bone Miner Res. 2015;30:1758–66.PubMedCrossRefGoogle Scholar
  173. 173.
    Kim JH, Yoon JW, Kim KW, et al. Increased dietary calcium intake is not associated with coronary artery calcification. Int J Cardiol. 2012;157:429–31.PubMedCrossRefGoogle Scholar
  174. 174.
    Anderson JJB, Kruszka B, Delaney JAC, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the multi-ethnic study of atherosclerosis (MESA). J Am Heart Assoc. 2016;5:e003815.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Bone and Muscle Health Research Group, Department of Medicine, Faculty of Medicine, Nursing and Health SciencesMonash University, Monash Medical CentreClaytonAustralia
  2. 2.Melbourne Medical School (Western Campus)University of MelbourneSt AlbansAustralia
  3. 3.Australian Institute for Musculoskeletal ScienceSt AlbansAustralia

Personalised recommendations