Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 141 No. 3536 (2011)

Calcium supplementation, osteoporosis and cardiovascular disease

  • M Kränzlin
Cite this as:
Swiss Med Wkly. 2011;141:w13260


Adequate intakes of calcium and vitamin D are essential preventive strategies and essential parts of any therapeutic regimen for osteoporosis. However, calcium supplementation is not without controversy and benefits on skeletal health need to be balanced against potential risks on cardiovascular disease. The published data so far suggest a potential detrimental effect of calcium supplement on cardiovascular health (i.e. myocardial infarction) although further prospective studies are needed to clarify the gradient of risk. Since food sources of calcium produce similar benefits on bone density as supplements and dietary calcium intake does not seem to be related with adverse cardiovascular effects, calcium intake from nutritional sources needs to be enforced. In patients with low calcium intake supplements are warranted aiming for a total calcium intake of 800 to 1000 mg/d together with adequate vitamin D replacement. Nevertheless we should keep in mind that for significant reduction in fracture risk, pharmacological treatment is mandatory in patients at risk of fractures irrespective of calcium and vitamin D supplementation.


  1. Bolland MJ, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010;341:c3691.
  2. Prince RL, et al. Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy. N Engl J Med. 1991;325(17):1189–95.
  3. Dawson-Hughes B, et al. A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med. 1990;323(13):878–83.
  4. Smith EL, et al. Calcium supplementation and bone loss in middle-aged women. Am J Clin Nutr. 1989;50(4):833–42.
  5. Prince R, et al. The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res. 1995;10(7):1068–75.
  6. Shea B, et al. Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Endocr Rev. 2002;23(4):552–9.
  7. Tang BM, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370(9588):657–66.
  8. Jones G, et al. Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ. 1994;309(6956):691–5.
  9. Ahlborg HG, et al. Bone loss and bone size after menopause. N Engl J Med. 2003;349(4):327–34.
  10. Reid IR, Bolland MJ, Grey A. Effect of calcium supplementation on hip fractures. Osteoporos Int. 2008;19(8):1119–23.
  11. Dawson-Hughes B, et al. 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(10):670–6.
  12. Chapuy MC, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327(23):1637–42.
  13. Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: A pragmatic population-based 3-year intervention study. J Bone Miner Res. 2004;19(3):370–8.
  14. Bischoff-Ferrari HA, et al. Effect of calcium supplementation on fracture risk: a double-blind randomized controlled trial. Am J Clin Nutr. 2008;87(6):1945–51.
  15. Reid IR, et al. Randomized controlled trial of calcium in healthy older women. Am J Med. 2006;119(9):777–85.
  16. Prince RL, et al. Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med. 2006;166(8):869–75.
  17. Jackson RD, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006;354(7):669–83.
  18. Grant AM, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet. 2005;365(9471):1621–8.
  19. Bischoff-Ferrari HA, et al. Milk intake and risk of hip fracture in men and women: a meta-analysis of prospective cohort studies. J Bone Miner Res. 2011;26(4):833–9.
  20. Boonen S, et al. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. 2007;92(4):1415–23.
  21. Yacowitz H, Fleischman AI, Bierenbaum ML. Effects of Oral Calcium Upon Serum Lipids in Man. Br Med J. 1965;1(5446):1352–4.
  22. Govers MJ, Van der Meet R. Effects of dietary calcium and phosphate on the intestinal interactions between calcium, phosphate, fatty acids, and bile acids. Gut. 1993;34(3):365–70.
  23. Christensen R, et al. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials. Obes Rev. 2009;10(4):475–86.
  24. Lanou AJ, Barnard ND. Dairy and weight loss hypothesis: an evaluation of the clinical trials. Nutr Rev. 2008;66(5):272–9.
  25. Reid IR, et al. Effects of calcium supplementation on lipids, blood pressure, and body composition in healthy older men: a randomized controlled trial. Am J Clin Nutr. 2010;91(1):131–9.
  26. Griffith LE, et al. The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials. Am J Hypertens. 1999;12(1 Pt 1):84–92.
  27. Reid IR, et al. Effects of calcium supplementation on body weight and blood pressure in normal older women: a randomized controlled trial. J Clin Endocrinol Metab. 2005;90(7):3824–9.
  28. van Mierlo LA, et al. Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials. J Hum Hypertens. 2006;20(8):571–80.
  29. Reid IR, et al. Cardiovascular effects of calcium supplementation. Osteoporos Int. 2011.
  30. Bolland MJ, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336(7638):262–6.
  31. Burckhardt P. Potential negative cardiovascular effects of calcium supplements. Osteoporos Int. 2011.
  32. Lewis JR, et al. Calcium supplementation and the risks of atherosclerotic vascular disease in older women: results of a 5-year RCT and a 4.5-year follow-up. J Bone Miner Res. 2011;26(1):35–41.
  33. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730–7.
  34. Melamed ML, et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629–37.
  35. Anderson JL, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106(7):963–8.
  36. Hsia J, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007;115(7):846–54.
  37. Bolland MJ, et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040.
  38. Wang L, et al. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010;152(5):315–23.
  39. Karp HJ, Ketola ME, Lamberg-Allardt CJ. Acute effects of calcium carbonate, calcium citrate and potassium citrate on markers of calcium and bone metabolism in young women. Br J Nutr. 2009;102(9):1341–7.
  40. Heller HJ, et al. Pharmacokinetic and pharmacodynamic comparison of two calcium supplements in postmenopausal women. J Clin Pharmacol. 2000;40(11):1237–44.
  41. Green JH, Booth C, Bunning R. Acute effect of high-calcium milk with or without additional magnesium, or calcium phosphate on parathyroid hormone and biochemical markers of bone resorption. Eur J Clin Nutr. 2003;57(1):61–8.
  42. Gibson RA, et al. The effect of dairy foods on CHD: a systematic review of prospective cohort studies. Br J Nutr. 2009;102(9):1267–75.
  43. Rubin MR, et al. Carotid artery plaque thickness is associated with increased serum calcium levels: the Northern Manhattan study. Atherosclerosis. 2007;194(2):426–32.
  44. Bolland MJ, et al. Abdominal aortic calcification on vertebral morphometry images predicts incident myocardial infarction. J Bone Miner Res. 2010;25(3):505–12.
  45. Slinin Y, et al. Serum calcium, phosphorus and cardiovascular events in post-menopausal women. Int J Cardiol. 2010.
  46. Lind L, et al. Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years. J Clin Epidemiol. 1997;50(8):967–73.
  47. Jorde R, et al. Serum calcium and cardiovascular risk factors and diseases: the Tromso study. Hypertension. 1999;34(3):484–90.
  48. Foley RN, et al. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156(3):556–63.
  49. Walker MD, Silverberg SJ. Cardiovascular aspects of primary hyperparathyroidism. J Endocrinol Invest. 2008;31(10):925–31.
  50. Russo D, et al. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int. 2007;72(10):1255–61.
  51. West SL, Swan VJ, Jamal SA. Effects of calcium on cardiovascular events in patients with kidney disease and in a healthy population. Clin J Am Soc Nephrol. 2010;5(Suppl 1):S41–7.
  52. Hilgard P. Experimental hypercalcaemia and whole blood clotting. J Clin Pathol. 1973;26(8):616–9.
  53. James MF, Roche AM. Dose-response relationship between plasma ionized calcium concentration and thrombelastography. J Cardiothorac Vasc Anesth. 2004;18(5):581–6.
  54. Neunteufl T, et al. Impairment of endothelium-independent vasodilation in patients with hypercalcemia. Cardiovasc Res. 1998;40(2):396–401.
  55. Baykan M, et al. Impairment of flow mediated vasodilatation of brachial artery in patients with primary hyperparathyroidism. Int J Cardiovasc Imaging. 2007;23(3):323–8.
  56. Nilsson IL, et al. Endothelial vasodilatory function and blood pressure response to local and systemic hypercalcemia. Surgery. 2001;130(6):986–90.
  57. Kanis JA, et al. Case finding for the management of osteoporosis with FRAX – assessment and intervention thresholds for the UK. Osteoporos Int. 2008;19(10):1395–408.
  58. Kanis JA, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2008;19(4):399–428.
  59. Kraenzlin ME, Meier C. Schlaglichter 2010: Neue Wege in der Diagnostik und Therapie der Osteoporose. Swiss Med Forum. 2011;11(3):25–8.
  60. Ross AC, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8.
  61. Lau EM, et al. Milk supplementation of the diet of postmenopausal Chinese women on a low calcium intake retards bone loss. J Bone Miner Res. 2001;16(9):1704–9.
  62. Cadogan J, et al. Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. BMJ. 1997;315(7118):1255–60.
  63. Bischoff-Ferrari HA, et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr. 2007;86(6):1780–90.