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The predicted lifetime costs and health consequences of calcium and vitamin D supplementation for fracture prevention—the impact of cardiovascular effects

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Abstract

Summary

Some studies indicate that calcium supplementation increases cardiovascular risk. We assessed whether such effects could counterbalance the fracture benefits from supplementation. Accounting for cardiovascular outcomes, calcium may cause net harm and would not be cost-effective. Clinicians may do well considering cardiovascular effects when prescribing calcium supplementation.

Introduction

Accounting for possible cardiovascular effect of calcium and vitamin D supplementation (CaD), the aims of this study were to assess whether CaD on balance would improve population health and to evaluate the cost-effectiveness of such supplementation.

Methods

We created a probabilistic Markov simulation model that was analysed at the individual patient level. We analysed 65-year-old Norwegian women with a 2.3 % 10-year risk of hip fracture and a 9.3 % risk of any major fracture according to the WHO fracture risk assessment tool (FRAX®). Consistent with a recent Cochrane review, we assumed that CaD reduces the risk of hip, vertebral, and wrist fractures by 16, 11, and 5 %, respectively. We included the increased risk of acute myocardial infarction (AMI) and stroke under a no-, medium-, and high-risk scenario.

Results

Assuming no cardiovascular effects, CaD supplementation produces improved health outcomes resulting in an incremental gain of 0.0223 quality-adjusted life years (QALYs) and increases costs by €322 compared with no treatment (cost-effectiveness ratio €14,453 per QALY gained). Assuming a Norwegian cost-effectiveness threshold of €60,000 per QALY, CaD is likely to be considered a cost-effective treatment alternative. In a scenario with a medium or high increased risk of cardiovascular events, CaD produces net health losses, respectively, −0.0572 and −0.0784 QALY at additional costs of €481 and €1033.

Conclusions

We conclude that the magnitude of potential cardiovascular side effects is crucial for the effectiveness and cost-effectiveness of CaD supplementation in elderly women.

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References

  1. 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(1–2):136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hansen L, Mathiesen AS, Vestergaard P, Ehlers LH, Petersen KD (2013) A health economic analysis of osteoporotic fractures: who carries the burden? Arch Osteoporos 8(1–2):126

    Article  PubMed  PubMed Central  Google Scholar 

  3. Boonen S, Rizzoli R, Meunier PJ, Stone M, Nuki G, Syversen U, Lehtonen-Veromaa M, Lips P, Johnell O, Reginster JY (2004) The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report. Osteoporos Int 15(7):511–519

    Article  CAS  PubMed  Google Scholar 

  4. Compston J, Bowring C, Cooper A, Cooper C, Davies C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P (2013) Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update 2013. Maturitas 75(4):392–396

    Article  CAS  PubMed  Google Scholar 

  5. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24(1):23–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Avenell A, Mak JC, O’Connell D (2014) Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev 4:CD000227

    PubMed  Google Scholar 

  7. Hiligsmann M, Ben Sedrine W, Bruyere O, Evers SM, Rabenda V, Reginster JY (2014) Cost-effectiveness of vitamin D and calcium supplementation in the treatment of elderly women and men with osteoporosis. European journal of public health. doi:10.1093/eurpub/cku119

  8. Li K, Kaaks R, Linseisen J, Rohrmann S (2012) Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart (British Cardiac Society) 98(12):920–925

    Article  CAS  Google Scholar 

  9. 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 (Clinical research ed) 336(7638):262–266

    Article  CAS  Google Scholar 

  10. 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 (Clinical research ed) 341:c3691

    Article  Google Scholar 

  11. Michaelsson K, Melhus H, Warensjo Lemming E, Wolk A, Byberg L (2013) Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ (Clinical research ed) 346:f228

    Google Scholar 

  12. Michaelsson K, Wolk A, Langenskiold S, Basu S, Warensjo Lemming E, Melhus H, Byberg L (2014) Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ (Clinical research ed) 349:g6015

    Google Scholar 

  13. 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 (Clinical research ed) 342:d2040

  14. Abrahamsen B, Sahota O (2011) Do calcium plus vitamin D supplements increase cardiovascular risk? BMJ (Clinical research ed) 342:d2080

    Article  Google Scholar 

  15. 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(6):763–771

    Article  CAS  Google Scholar 

  16. Rojas-Fernandez CH, Maclaughlin EJ, Dore NL, Ebsary S (2012) Assessing the potential adverse consequences of supplemental calcium on cardiovascular outcomes: should we change our approach to bone health? Ann Pharmacother 46(5):696–702

    Article  PubMed  Google Scholar 

  17. Nordin BE, Lewis JR, Daly RM, Horowitz J, Metcalfe A, Lange K, Prince RL (2011) The calcium scare—what would Austin Bradford Hill have thought? Osteoporos Int 22(12):3073–3077

    Article  CAS  PubMed  Google Scholar 

  18. Prince RL, Nordin C, Lewis JR, Metcalfe A, Daly RM (2012) Problems with epidemiological approach and conclusions. Heart (British Cardiac Society) 98(23):1751, author reply 1751–1752

    Article  Google Scholar 

  19. Prentice RL, Pettinger MB, Jackson RD, Wactawski-Wende J, Lacroix AZ, Anderson GL, Chlebowski RT, Manson JE, Van Horn L, Vitolins MZ, Datta M, LeBlanc ES, Cauley JA, Rossouw JE (2013) Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 24(2):567–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rothman KJ (2010) Curbing type I and type II errors. Eur J Epidemiol 25(4):223–224

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25(10):2359–2381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hagen G, Wisløff T, Falch J, Lofthus C, Frihagen F, Wensaas KA, Granum L, Nevjar J, Kristiansen IS, Klemp M (2011) Efficacy and cost-effectiveness of alendronate for the prevention of fractures in postmenopausal women in Norway. Rapport fra Kunnskapssenteret vol 10–2011. Kunnskapssenteret http://www.kunnskapssenteret.no/Publikasjoner/Efficacy+and+cost-effectiveness+of+alendronate+for+the+prevention+of+fractures+in+postmenopausal+women+in+Norway.12475.cms

  23. Wisloff T, Hagen G, Klemp M (2014) Economic evaluation of warfarin, dabigatran, rivaroxaban, and apixaban for stroke prevention in atrial fibrillation. Pharmacoeconomics 32(6):601–612

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wisloff T, Selmer RM, Halvorsen S, Fretheim A, Norheim OF, Kristiansen IS (2012) Choice of generic antihypertensive drugs for the primary prevention of cardiovascular disease—a cost-effectiveness analysis. BMC Cardiovasc Disord 12:26

    Article  PubMed  PubMed Central  Google Scholar 

  25. Boyd CM, Singh S, Varadhan R, Weiss CO, Sharma R, Bass EB, Puhan MA (2012) Methods for benefit and harm assessment in systematic reviews. Methods research report (Prepared by Johns Hopkins University Evidence-based Practice Centre under contract No. 290-2007-10061-I). AHRQ publication No. 12 (13)-EHC150-EF. Rockville MD: Agency for healthcare research and quality, November 2012

  26. Burstrom K, Johannesson M, Diderichsen F (2001) Health-related quality of life by disease and socio-economic group in the general population in Sweden. Health Policy 55(1):51–69

    Article  CAS  PubMed  Google Scholar 

  27. Ara R, Brazier JE (2010) Populating an economic model with health state utility values: moving toward better practice. Value Health 13(5):509–518

    Article  PubMed  Google Scholar 

  28. Wisloff T, Selmer RM, Halvorsen S, Kristiansen IS (2008) Norwegian Cardiovascular Disease Model (NorCaD) – a simulation model for estimating health benefits and cost consequences of cardiovascular interventions. http://www.kunnskapssenteret.no/publikasjoner/norwegian-cardiovascular-disease-model-norcad-a-simulation-model-for-estimating-health-benefits-and-cost-consequences-of-cardiovascular-interventions

  29. Prestmo A, Hagen G, Sletvold O, Helbostad JL, Thingstad P, Taraldsen K, Lydersen S, Halsteinli V, Saltnes T, Lamb SE, Johnsen LG, Saltvedt I (2015) Comprehensive geriatric care for patients with hip fractures: a prospective, randomised, controlled trial. The Lancet 385:1623–1633

  30. Recommendations for the economic evaluation of new interventions in the Norwegian health sector. (2012). The Norwegian Directorate of Health, vol IS-1985. Oslo, Norway

  31. Health Effects in Economic Analyses (2007). The Norwegian Directorate of Health, vol IS-1435. Oslo, Norway

  32. Briggs A, Claxton K, Schulpher M (2006) Decision Modelling for Health Economic Evaluation. Handbooks in Health Economic Evaluation. Oxford University Press, New York

  33. Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y (2013) Dietary and supplemental calcium intake and cardiovascular disease mortality: the National Institutes of Health-AARP diet and health study. JAMA Intern Med 173(8):639–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 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:CD007470

    PubMed  Google Scholar 

  35. Vestergaard P, Rejnmark L, Mosekilde L (2007) Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture complications. Osteoporos Int 18(12):1583–1593

    Article  CAS  PubMed  Google Scholar 

  36. Morin S, Lix LM, Azimaee M, Metge C, Caetano P, Leslie WD (2011) Mortality rates after incident non-traumatic fractures in older men and women. Osteoporos Int 22(9):2439–2448

    Article  CAS  PubMed  Google Scholar 

  37. Hiligsmann M, Rabenda V, Gathon HJ, Ethgen O, Reginster JY (2010) Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif Tissue Int 86(3):202–210

    Article  CAS  Google Scholar 

  38. Weinstein M, O’Brien B, Hornberger J, Jackson J, Johannesson M, McCabe C, Luce B (2003) Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR task force on good research practices - Modeling studies. Value Health 6(1):9–17

    Article  PubMed  Google Scholar 

  39. Si L, Winzenberg TM, Palmer AJ (2014) A systematic review of models used in cost-effectiveness analyses of preventing osteoporotic fractures. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, vol 25, pp 51–60

  40. Willis MS (2002) The health economics of calcium and vitamin D3 for the prevention of osteoporotic hip fractures in Sweden. Int J Technol Assess Health Care 18(4):791–807

    PubMed  Google Scholar 

  41. Ethgen O, Hiligsmann M, Burlet N, Reginster JY (2015) Cost-effectiveness of personalized supplementation with vitamin D-rich dairy products in the prevention of osteoporotic fractures. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, vol 73. Oslo, Norway, p 48

  42. Stoen RO, Nordsletten L, Meyer HE, Frihagen JF, Falch JA, Lofthus CM (2012) Hip fracture incidence is decreasing in the high incidence area of Oslo, Norway. Osteoporos Int 23(10):2527–2534

    Article  CAS  PubMed  Google Scholar 

  43. Kanis JA, Johnell O, Oden A, Borgstrom F, Zethraeus N, De Laet C, Jonsson B (2004) The risk and burden of vertebral fractures in Sweden. Osteoporos Int 15(1):20–26

    Article  CAS  PubMed  Google Scholar 

  44. Lofthus CM, Frihagen F, Meyer HE, Nordsletten L, Melhuus K, Falch JA (2008) Epidemiology of distal forearm fractures in Oslo, Norway. Osteoporos Int 19(6):781–786

    Article  CAS  PubMed  Google Scholar 

  45. Drageset J, Eide GE, Ranhoff AH (2013) Mortality in nursing home residents without cognitive impairment and its relation to self-reported health-related quality of life, sociodemographic factors, illness variables and cancer diagnosis: a 5-year follow-up study. Qual Life Res 22(2): 317–325

    Article  PubMed  Google Scholar 

  46. Morin S, Lix LM, Azimaee M, Metge C, Majumdar SR, Leslie WD (2012) Institutionalization following incident non-traumatic fractures in community-dwelling men and women. Osteoporos Int 23(9):2381–2386

    Article  CAS  PubMed  Google Scholar 

  47. Peasgood T, Herrmann K, Kanis JA, Brazier JE (2009) An updated systematic review of Health State Utility Values for osteoporosis related conditions. Osteoporos Int 20(6):853–868

    Article  CAS  PubMed  Google Scholar 

  48. Nowels D, McGloin J, Westfall JM, Holcomb S (2005) Validation of the EQ-5D quality of life instrument in patients after myocardial infarction. Qual Life Res 14(1):95–105

    Article  PubMed  Google Scholar 

  49. Lee HY, Hwang JS, Jeng JS, Wang JD (2010) Quality-adjusted life expectancy (QALE) and loss of QALE for patients with ischemic stroke and intracerebral hemorrhage: a 13-year follow-up. Stroke 41(4):739–744

    Article  PubMed  Google Scholar 

  50. Kontodimopoulos N, Argiriou M, Theakos N, Niakas D (2011) The impact of disease severity on EQ-5D and SF-6D utility discrepancies in chronic heart failure. Eur J Health Econ 12(4):383–391

    Article  PubMed  Google Scholar 

  51. Makai P, Beckebans F, van Exel J, Brouwer WB (2014) Quality of life of nursing home residents with dementia: validation of the German version of the ICECAP-O. PLoS One 9(3):e92016

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We would like to acknowledge funding for this project from St. Olav’s Hospital, Trondheim University Hospital, and the Norwegian University of Science and Technology. Further, we would like to acknowledge The Norwegian Knowledge Centre for the Health Care Services (NOKC) for facilitating the development of earlier decision models, which we have built on in this project.

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Correspondence to G. Hagen.

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Conflicts of interest

Unrelated to this study, we report the following conflicts: GH has received payment for one lecture held for Amgen on the cost of hip fractures in Norway. TW has received payment from the consulting firm Oslo Economics for work performed for Amgen not related to osteoporosis. ISK has received honoraria from Merck related to osteoporosis and from Amgen not related to osteoporosis.

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Hagen, G., Wisløff, T. & Kristiansen, I.S. The predicted lifetime costs and health consequences of calcium and vitamin D supplementation for fracture prevention—the impact of cardiovascular effects. Osteoporos Int 27, 2089–2098 (2016). https://doi.org/10.1007/s00198-016-3495-9

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