Advertisement

Osteoporosis International

, Volume 28, Issue 2, pp 447–462 | Cite as

The role of calcium supplementation in healthy musculoskeletal ageing

An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF)
  • N. C. Harvey
  • E. Biver
  • J.-M. Kaufman
  • J. Bauer
  • J. Branco
  • M. L. Brandi
  • O. Bruyère
  • V. Coxam
  • A. Cruz-Jentoft
  • E. Czerwinski
  • H. Dimai
  • P. Fardellone
  • F. Landi
  • J.-Y. Reginster
  • B. Dawson-Hughes
  • J. A. Kanis
  • R. Rizzoli
  • C. CooperEmail author
Review

Abstract

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

Keywords

Calcium supplementation Fracture reduction Myocardial infarction Vitamin D supplementation 

Notes

Acknowledgments

The meeting was funded by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), a Belgian not-for-profit organisation.

Compliance with ethical standards

Conflict of interest

N. Harvey has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare and Internis Pharma. C. Cooper has received consultancy, lecture fees and honoraria from AMGEN, GSK, Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, Medtronic and Roche. V. Coxam has received Institutional funding and honoraria for an oral intervention at a scientific meeting Le Centre National Interprofessionnel de l’Economie Laitière (CNIEL). J.-M. Kaufman has received speaker or consultant fees from Amgen, Eli Lilly, Servier. E. Czerwinski has received research support and lecture fees from Amgen. O. Bruyere has received grant support from IBSA, MSD, Nutraveris, Novartis, Pfizer, Rottapharm, Servier, and Theramex; consulting or lecture fees from Bayer, Genevrier, IBSA, Rottapharm, Servier, SMB and TRB Chemedica. B. Dawson-Hughes has received research funding and consultancy from Pfizer Inc. E. Biver, J. Bauer, J. Branco, M.L. Brandi, A. Cruz-Jentoft, H. Dimai, P. Fardellone, F. Landi, J.Y. Reginster, J.A. Kanis and R. Rizzoli declare that they have no conflict of interest. ESCEO and IOF disclosures: none in relation to this paper.

References

  1. 1.
    Seeman E (2008) Structural basis of growth-related gain and age-related loss of bone strength. Rheumatology (Oxford) 47(Suppl 4):iv2–iv8Google Scholar
  2. 2.
    Rozenberg S, Body JJ, Bruyere O et al (2016) Effects of dairy products consumption on health: benefits and beliefs—a commentary from the Belgian Bone Club and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases. Calcif Tissue Int 98:1–17CrossRefPubMedGoogle Scholar
  3. 3.
    Bruyere O, Cavalier E, Souberbielle JC, Bischoff-Ferrari HA, Beaudart C, Buckinx F, Reginster JY, Rizzoli R (2014) Effects of vitamin D in the elderly population: current status and perspectives. Archives of public health = Archives belges de sante publique 72:32CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Rizzoli R, Boonen S, Brandi ML, Bruyere O, Cooper C, Kanis JA, Kaufman JM, Ringe JD, Weryha G, Reginster JY (2013) Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Curr Med Res Opin 29:305–313CrossRefPubMedGoogle Scholar
  5. 5.
    Ethgen O, Hiligsmann M, Burlet N, Reginster JY (2016) Cost-effectiveness of personalized supplementation with vitamin D-rich dairy products in the prevention of osteoporotic fractures. Osteoporos Int 27:301–308CrossRefPubMedGoogle Scholar
  6. 6.
    Cianferotti L, Parri S, Gronchi G, Rizzuti C, Fossi C, Black DM, Brandi ML (2015) Changing patterns of prescription in vitamin D supplementation in adults: analysis of a regional dataset. Osteoporos Int 26:2695–2702CrossRefPubMedGoogle Scholar
  7. 7.
    Kuo IY, Ehrlich BE (2015) Signaling in muscle contraction. Cold Spring Harb Perspect Biol 7:a006023CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gehlert S, Bloch W, Suhr F (2015) Ca2+-dependent regulations and signaling in skeletal muscle: from electro-mechanical coupling to adaptation. Int J Mol Sci 16:1066–1095CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rizzoli R, Stevenson JC, Bauer JM, van Loon LJ, Walrand S, Kanis JA, Cooper C, Brandi ML, Diez-Perez A, Reginster JY (2014) The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women: a consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO. Maturitas 79:122–132CrossRefPubMedGoogle Scholar
  10. 10.
    Harvey N, Dennison E, Cooper C (2010) Osteoporosis: impact on health and economics. Nat Rev Rheumatol 6:99–105CrossRefPubMedGoogle Scholar
  11. 11.
    Fielding RA, Vellas B, Evans WJ et al (2011) Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 12:249–256CrossRefPubMedGoogle Scholar
  12. 12.
    Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jonsson B, Kanis JA (2013) 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 8:136CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Silk LN, Greene DA, Baker MK (2015) The effect of calcium or calcium and vitamin D supplementation on bone mineral density in healthy males: a systematic review and meta-analysis. International journal of sport nutrition and exercise metabolism 25:510–524CrossRefPubMedGoogle Scholar
  14. 14.
    Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S (2010) Reducing fracture risk with calcium and vitamin D. Clin Endocrinol 73:277–285CrossRefGoogle Scholar
  15. 15.
    Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY (2006) Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 78:257–270CrossRefPubMedGoogle Scholar
  16. 16.
    Tai V, Leung W, Grey A, Reid IR, Bolland MJ (2015) Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ 351:h4183CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A (2007) 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 370:657–666CrossRefPubMedGoogle Scholar
  18. 18.
    Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA et al (2007) 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 86:1780–1790PubMedGoogle Scholar
  19. 19.
    DIPART Group (2010) Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340:b5463Google Scholar
  20. 20.
    Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR (2015) Calcium intake and risk of fracture: systematic review. BMJ 351:h4580CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC, Wang DD (2016) Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int 27:367–376CrossRefPubMedGoogle Scholar
  22. 22.
    Prentice RL, Pettinger MB, Jackson RD et al (2013) Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 24:567–580CrossRefPubMedGoogle Scholar
  23. 23.
    Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–1642CrossRefPubMedGoogle Scholar
  24. 24.
    Grant AM, Avenell A, Campbell MK et al (2005) 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 365:1621–1628CrossRefPubMedGoogle Scholar
  25. 25.
    Institute of Medicine of the National Academies, National Academy of Sciences, Washington, DC (2011). Dietary Reference Intakes for Calcium and Vitamin D (report)Google Scholar
  26. 26.
    Curtis EM, Moon RJ, Dennison EM, Harvey NC, Cooper C (2015) Recent advances in the pathogenesis and treatment of osteoporosis. Clinical medicine (London, England) 15(Suppl 6):s92–s96CrossRefGoogle Scholar
  27. 27.
    McCloskey EV, Beneton M, Charlesworth D et al (2007) Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res 22:135–141CrossRefPubMedGoogle Scholar
  28. 28.
    Bonnick S, Broy S, Kaiser F, Teutsch C, Rosenberg E, DeLucca P, Melton M (2007) Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density. Curr Med Res Opin 23:1341–1349CrossRefPubMedGoogle Scholar
  29. 29.
    Hirata D, Nagashima T, Saito S, Okazaki H, Kano S, Minota S (2002) Elevated muscle enzymes in a patient with severe hypocalcemia mimicking polymyositis. Modern rheumatology / the Japan Rheumatism Association 12:186–189CrossRefGoogle Scholar
  30. 30.
    Thabit H, Barry M, Sreenan S, Smith D (2011) Proximal myopathy in lacto-vegetarian Asian patients responding to vitamin D and calcium supplement therapy - two case reports and review of the literature. J Med Case Rep 5:178CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, Petermans J, Reginster JY, Bruyere O (2014) The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 99:4336–4345CrossRefPubMedGoogle Scholar
  32. 32.
    Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, Wong JB, Egli A, Kiel DP, Henschkowski J (2009) Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ (Clinical research ed) 339:b3692CrossRefGoogle Scholar
  33. 33.
    Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB (2004) Effect of vitamin D on falls: a meta-analysis. JAMA 291:1999–2006CrossRefPubMedGoogle Scholar
  34. 34.
    Jackson C, Gaugris S, Sen SS, Hosking D (2007) The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM : monthly journal of the Association of Physicians 100:185–192CrossRefPubMedGoogle Scholar
  35. 35.
    Kalyani RR, Stein B, Valiyil R, Manno R, Maynard JW, Crews DC (2010) Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. J Am Geriatr Soc 58:1299–1310CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    LeBlanc ES, Chou R (2015) VItamin d and falls—fitting new data with current guidelines. JAMA Intern Med 175:712–713CrossRefPubMedGoogle Scholar
  37. 37.
    Michael YL, Whitlock EP, Lin JS, Fu R, O’Connor EA, Gold R (2010) Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 153:815–825CrossRefPubMedGoogle Scholar
  38. 38.
    Murad MH, Elamin KB, Abu Elnour NO et al (2011) Clinical review: the effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 96:2997–3006CrossRefPubMedGoogle Scholar
  39. 39.
    O’Donnell S, Moher D, Thomas K, Hanley DA, Cranney A (2008) Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls. J Bone Miner Metab 26:531–542CrossRefPubMedGoogle Scholar
  40. 40.
    Richy F, Dukas L, Schacht E (2008) Differential effects of D-hormone analogs and native vitamin D on the risk of falls: a comparative meta-analysis. Calcif Tissue Int 82:102–107CrossRefPubMedGoogle Scholar
  41. 41.
    Cameron ID, Gillespie LD, Robertson MC, Murray GR, Hill KD, Cumming RG, Kerse N (2012) Interventions for preventing falls in older people in care facilities and hospitals. Cochrane Database Syst Rev 12:CD005465PubMedGoogle Scholar
  42. 42.
    Cameron ID, Murray GR, Gillespie LD, Robertson MC, Hill KD, Cumming RG, Kerse N (2010) Interventions for preventing falls in older people in nursing care facilities and hospitals. Cochrane Database Syst Rev Cd005465Google Scholar
  43. 43.
    Bolland MJ, Grey A, Gamble GD, Reid IR (2014) Vitamin D supplementation and falls: a trial sequential meta-analysis. The lancet Diabetes & endocrinology 2:573–580CrossRefGoogle Scholar
  44. 44.
    Dukas L, Bischoff HA, Lindpaintner LS, Schacht E, Birkner-Binder D, Damm TN, Thalmann B, Stahelin HB (2004) Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. J Am Geriatr Soc 52:230–236CrossRefPubMedGoogle Scholar
  45. 45.
    Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, Rowe BH (2009) Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev Cd007146Google Scholar
  46. 46.
    Gillespie LD, Robertson MC, Gillespie WJ, Sherrington C, Gates S, Clemson LM, Lamb SE (2012) Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev 9:CD007146Google Scholar
  47. 47.
    Uusi-Rasi K, Patil R, Karinkanta S, Kannus P, Tokola K, Lamberg-Allardt C, Sievanen H (2015) Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. JAMA Intern Med 175:703–711CrossRefPubMedGoogle Scholar
  48. 48.
    Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 303:1815–1822CrossRefPubMedGoogle Scholar
  49. 49.
    Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, Dick W, Willett WC, Egli A (2016) Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med 176:175–183CrossRefPubMedGoogle Scholar
  50. 50.
    Gallagher JC (2016) Vitamin D and falls—the dosage conundrum. Nat Rev EndocrinolGoogle Scholar
  51. 51.
    Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, Gamble GD, Grey A, Reid IR (2008) Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 336:262–266CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C (2014) Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 1:CD007470Google Scholar
  53. 53.
    Lewis JR, Zhu K, Prince RL (2012) Adverse events from calcium supplementation: relationship to errors in myocardial infarction self-reporting in randomized controlled trials of calcium supplementation. J Bone Miner Res 27:719–722CrossRefPubMedGoogle Scholar
  54. 54.
    Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Prince RL, Devine A, Dhaliwal SS, Dick IM (2006) 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 166:869–875CrossRefPubMedGoogle Scholar
  56. 56.
    Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR (2011) 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 342:d2040CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Lewis JR, Radavelli-Bagatini S, Rejnmark L, Chen JS, Simpson JM, Lappe JM, Mosekilde L, Prentice RL, Prince RL (2015) The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res 30:165–175CrossRefPubMedGoogle Scholar
  58. 58.
    Rosamond WD, Sprafka JM, McGovern PG, Nelson M, Luepker RV (1995) Validation of self-reported history of acute myocardial infarction: experience of the Minnesota Heart Survey Registry. Epidemiology 6:67–69CrossRefPubMedGoogle Scholar
  59. 59.
    Colditz GA, Martin P, Stampfer MJ, Willett WC, Sampson L, Rosner B, Hennekens CH, Speizer FE (1986) Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am J Epidemiol 123:894–900CrossRefPubMedGoogle Scholar
  60. 60.
    Bolland MJ, Grey A, Reid IR (2013) Calcium supplements and cardiovascular risk: 5 years on. Therapeutic advances in drug safety 4:199–210CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Larsen ER, Mosekilde L, Foldspang A (2004) 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 19:370–378CrossRefPubMedGoogle Scholar
  62. 62.
    Mao PJ, Zhang C, Tang L, Xian YQ, Li YS, Wang WD, Zhu XH, Qiu HL, He J, Zhou YH (2013) Effect of calcium or vitamin D supplementation on vascular outcomes: a meta-analysis of randomized controlled trials. Int J Cardiol 169:106–111CrossRefPubMedGoogle Scholar
  63. 63.
    Hsia J, Heiss G, Ren H et al (2007) Calcium/vitamin D supplementation and cardiovascular events. Circulation 115:846–854CrossRefPubMedGoogle Scholar
  64. 64.
    Cauley JA, Chlebowski RT, Wactawski-Wende J, Robbins JA, Rodabough RJ, Chen Z, Johnson KC, O’Sullivan MJ, Jackson RD, Manson JE (2013) Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women’s Health Initiative. J Women’s Health 22:915–929CrossRefGoogle Scholar
  65. 65.
    Manson JE, Allison MA, Carr JJ et al (2010) Calcium/vitamin D supplementation and coronary artery calcification in the Women’s Health Initiative. Menopause 17:683–691PubMedPubMedCentralGoogle Scholar
  66. 66.
    Rejnmark L, Avenell A, Masud T, et al. (2012) Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab 97:2670–2681Google Scholar
  67. 67.
    Avenell A, MacLennan GS, Jenkinson DJ et al (2012) Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial. J Clin Endocrinol Metab 97:614–622CrossRefPubMedGoogle Scholar
  68. 68.
    Reid IR, Bolland MJ (2008) Calcium supplementation and vascular disease. Climacteric : the journal of the International Menopause Society 11:280–286CrossRefGoogle Scholar
  69. 69.
    Heaney RP, Kopecky S, Maki KC, Hathcock J, Mackay D, Wallace TC (2012) A review of calcium supplements and cardiovascular disease risk. Adv Nutr (Bethesda, Md) 3:763–771CrossRefGoogle Scholar
  70. 70.
    Lind L, Skarfors E, Berglund L, Lithell H, Ljunghall S (1997) Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years. J Clin Epidemiol 50:967–973CrossRefPubMedGoogle Scholar
  71. 71.
    Jorde R, Sundsfjord J, Fitzgerald P, Bonaa KH (1999) Serum calcium and cardiovascular risk factors and diseases: the Tromso study. Hypertension 34:484–490CrossRefPubMedGoogle Scholar
  72. 72.
    Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G (2005) Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633CrossRefPubMedGoogle Scholar
  73. 73.
    Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM, Vasan RS (2007) Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 167:879–885CrossRefPubMedGoogle Scholar
  74. 74.
    Foley RN, Collins AJ, Ishani A, Kalra PA (2008) Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 156:556–563CrossRefPubMedGoogle Scholar
  75. 75.
    Larsson TE, Olauson H, Hagstrom E, Ingelsson E, Arnlov J, Lind L, Sundstrom J (2010) Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community. Arterioscler Thromb Vasc Biol 30:333–339CrossRefPubMedGoogle Scholar
  76. 76.
    Slinin Y, Blackwell T, Ishani A, Cummings SR, Ensrud KE (2011) Serum calcium, phosphorus and cardiovascular events in post-menopausal women. Int J Cardiol 149:335–340CrossRefPubMedGoogle Scholar
  77. 77.
    Rohrmann S, Garmo H, Malmstrom H, Hammar N, Jungner I, Walldius G, Van Hemelrijck M (2016) Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study. Atherosclerosis 251:85–93CrossRefPubMedGoogle Scholar
  78. 78.
    Kim WS, Lee DH, Youn HJ (2013) Calcium-phosphorus product concentration is a risk factor of coronary artery disease in metabolic syndrome. Atherosclerosis 229:253–257CrossRefPubMedGoogle Scholar
  79. 79.
    Gronhoj MH, Gerke O, Mickley H, Steffensen FH, Lambrechtsen J, Sand NP, Rasmussen LM, Olsen MH, Diederichsen A (2016) Associations between calcium-phosphate metabolism and coronary artery calcification; a cross sectional study of a middle-aged general population. Atherosclerosis 251:101–108CrossRefPubMedGoogle Scholar
  80. 80.
    Foley RN, Collins AJ, Herzog CA, Ishani A, Kalra PA (2009) Serum phosphorus levels associate with coronary atherosclerosis in young adults. Journal of the American Society of Nephrology : JASN 20:397–404CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Shiraki M, Sugimoto T, Nakamura T (2013) Effects of a single injection of teriparatide on bone turnover markers in postmenopausal women. Osteoporos Int 24:219–226CrossRefPubMedGoogle Scholar
  82. 82.
    Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441CrossRefPubMedGoogle Scholar
  83. 83.
    Nardi A, Ventura L, Cozzi L, Tonini G, Zennaro R, Celi M, Ramazzina E (2013) The bone anabolic therapy. Aging Clin Exp Res 25(Suppl 1):S121–S124CrossRefPubMedGoogle Scholar
  84. 84.
    Reginster JY, Brandi ML, Cannata-Andia J, Cooper C, Cortet B, Feron JM, Genant H, Palacios S, Ringe JD, Rizzoli R (2015) The position of strontium ranelate in today’s management of osteoporosis. Osteoporos Int 26:1667–1671CrossRefPubMedGoogle Scholar
  85. 85.
    Otsuka F, Yasuda S, Noguchi T, Ishibashi-Ueda H (2016) Pathology of coronary atherosclerosis and thrombosis. Cardiovascular diagnosis and therapy 6:396–408CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Reid IR, Mason B, Horne A, Ames R, Clearwater J, Bava U, Orr-Walker B, Wu F, Evans MC, Gamble GD (2002) Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. Am J Med 112:343–347CrossRefPubMedGoogle Scholar
  87. 87.
    Reid IR, Ames R, Mason B, Bolland MJ, Bacon CJ, Reid HE, Kyle C, Gamble GD, Grey A, Horne A (2010) Effects of calcium supplementation on lipids, blood pressure, and body composition in healthy older men: a randomized controlled trial. Am J Clin Nutr 91:131–139CrossRefPubMedGoogle Scholar
  88. 88.
    Denke MA, Fox MM, Schulte MC (1993) Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men. J Nutr 123:1047–1053PubMedGoogle Scholar
  89. 89.
    Bell L, Halstenson CE, Halstenson CJ, Macres M, Keane WF (1992) Cholesterol-lowering effects of calcium carbonate in patients with mild to moderate hypercholesterolemia. Arch Intern Med 152:2441–2444CrossRefPubMedGoogle Scholar
  90. 90.
    Griffith LE, Guyatt GH, Cook RJ, Bucher HC, Cook DJ (1999) The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials. Am J Hypertens 12:84–92CrossRefPubMedGoogle Scholar
  91. 91.
    Floege J (2016) Phosphate binders in chronic kidney disease: a systematic review of recent data. Journal of nephrology 29:329–340CrossRefPubMedGoogle Scholar
  92. 92.
    Shroff RC, McNair R, Skepper JN, Figg N, Schurgers LJ, Deanfield J, Rees L, Shanahan CM (2010) Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. Journal of the American Society of Nephrology : JASN 21:103–112CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  • N. C. Harvey
    • 1
    • 2
  • E. Biver
    • 3
  • J.-M. Kaufman
    • 4
  • J. Bauer
    • 5
  • J. Branco
    • 6
  • M. L. Brandi
    • 7
  • O. Bruyère
    • 8
  • V. Coxam
    • 9
    • 10
  • A. Cruz-Jentoft
    • 11
  • E. Czerwinski
    • 12
  • H. Dimai
    • 13
  • P. Fardellone
    • 14
  • F. Landi
    • 15
  • J.-Y. Reginster
    • 16
  • B. Dawson-Hughes
    • 17
  • J. A. Kanis
    • 18
    • 19
  • R. Rizzoli
    • 3
  • C. Cooper
    • 1
    • 2
    • 20
    Email author
  1. 1.MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK
  2. 2.NIHR Southampton Biomedical Research CentreSouthamptonUK
  3. 3.Service of Bone DiseasesUniversity Hospitals GenevaGenevaSwitzerland
  4. 4.Department of Internal Medicine, section EndocrinologyGhent UniversityGhentBelgium
  5. 5.Department of Geriatric Medicine, KlinikumCarl von Ossietzky UniversityOldenburgGermany
  6. 6.CEDOC - NOVA Medical School, UNL and Rheumatology DepartmentCHLO/Hospital Egas MonizLisbonPortugal
  7. 7.Head, Bone and Mineral Metabolic Unit, Department of Surgery and Translational MedicineUniversity of FlorenceFlorenceItaly
  8. 8.Department of Public Health, Epidemiology and Health EconomicsUniversity of LiègeLiègeBelgium
  9. 9.INRA, UMR 1019, UNH, CRNH AuvergneClermont-FerrandFrance
  10. 10.Clermont Université, Université d’Auvergne, Unité de Nutrition HumaineClermont-FerrandFrance
  11. 11.Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (Irycis)MadridSpain
  12. 12.Department of Bone and Joint Diseases, Faculty of Health Sciences, Krakow Medical CentreJagiellonian UniversityKrakowPoland
  13. 13.Department of Internal Medicine, Division of Endocrinology and DiabetologyMedical University of GrazGrazAustria
  14. 14.CHU Amiens, Université Picardie - Jules Verne, INSERM U 1088AmiensFrance
  15. 15.Geriatric DepartmentCatholic University of Sacred HeartMilanItaly
  16. 16.Department of Public Health, Epidemiology and Health EconomicsUniversity of LiègeLiègeBelgium
  17. 17.Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA
  18. 18.Centre for Metabolic Bone DiseasesUniversity of SheffieldSheffieldUK
  19. 19.Institute for Health and AgeingCatholic University of AustraliaMelbourneAustralia
  20. 20.Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research CentreUniversity of OxfordOxfordUK

Personalised recommendations